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Volume 31,Issue 6,2024 Table of Contents
2024, 31(6):541-551.
DOI: 10.3872/j.issn.1007-385X.2024.06.001
Abstract:
RUNX, a member of transcription factor family, plays an important role in the regulation of mammalian cell proliferation, differentiation, lineage development, osteogenesis and neurogenesis. The studies of RUNX have revealed the diversity of its function and its role in tumor genesis and progression. RUNX family members have different functional manifestations in different types of tumors and have different levels of association with various components in the tumor microenvironment. RUNX family members regulate the lineage development and differentiation of CD4+ helper T (Th) cells and CD8+ cytotoxic T lymphocytes (CTLs) in the tumor microenvironment, modulate the phenotype, differentiation, and survival of tissue-resident T-lymphocytes, and drive the proliferation activation and tissue-resident of NK-cells. RUNX family deletion leads to MDSC proliferation and maturation activation, which induces a tumor immunosuppressive icroenvironment. The expression of RUNX family members also significantly correlates with the degree of infiltration of tumor-associated fibroblasts (CAFs) in the tumor microenvironment, the infiltration of different immune cells, immune checkpoint gene expression, and drug sensitivity, which could serve as potential prognostic markers of tumors and as targets for tumor immunotherapy, and the combination with CAR-T cell therapy has great potential for application. This review focuses on the basic structure and function of RUNX and its role in the regulation of various components in tumor immunity and microenvironment, aiming to provide a new perspective for tumor immunotherapy with RUNX as the main target in the future.
RUNX, a member of transcription factor family, plays an important role in the regulation of mammalian cell proliferation, differentiation, lineage development, osteogenesis and neurogenesis. The studies of RUNX have revealed the diversity of its function and its role in tumor genesis and progression. RUNX family members have different functional manifestations in different types of tumors and have different levels of association with various components in the tumor microenvironment. RUNX family members regulate the lineage development and differentiation of CD4+ helper T (Th) cells and CD8+ cytotoxic T lymphocytes (CTLs) in the tumor microenvironment, modulate the phenotype, differentiation, and survival of tissue-resident T-lymphocytes, and drive the proliferation activation and tissue-resident of NK-cells. RUNX family deletion leads to MDSC proliferation and maturation activation, which induces a tumor immunosuppressive icroenvironment. The expression of RUNX family members also significantly correlates with the degree of infiltration of tumor-associated fibroblasts (CAFs) in the tumor microenvironment, the infiltration of different immune cells, immune checkpoint gene expression, and drug sensitivity, which could serve as potential prognostic markers of tumors and as targets for tumor immunotherapy, and the combination with CAR-T cell therapy has great potential for application. This review focuses on the basic structure and function of RUNX and its role in the regulation of various components in tumor immunity and microenvironment, aiming to provide a new perspective for tumor immunotherapy with RUNX as the main target in the future.
2024, 31(6):552-557.
DOI: 10.3872/j.issn.1007-385X.2024.06.002
Abstract:
Objective: To explore the potential of colon cancer cell membrane-coated copper-based metal-organic frameworks (MOF@CCM) in anti-tumor activities and promotion of tissue healing. Methods: Copper (Ⅱ) 1, 3, 5-benzenetricarboxylate copperbased metal-organic framework (HKUST-1) was constructed, and coated with colon cancer cell CT26 membrane on its outer layer to obtain MOF@CCM, which was physically characterized. The biocompatibility of MOF@CCM was determined by CCK-8 assay, and the effect of MOF@CCM on the proportion of DC2.4 maturation was analyzed by flow cytometry to verify the potential of MOF@CCM in activating immune cells. Angiogenesis experiments was used to verify the potential of MOF@CCM in promoting HUVEC to form blood vessels. Results: MOF@CCM was successfully synthesized. Transmission electron microscopy showed that its shape was approximately circular and had an obvious core-shell structure. The average particle size of MOF@CCM was (150.5±7.89) nm, and the average Zeta potential was -(5.12±1.67) mV. The results of in vitro experiments showed that compared with the control group, MOF@CCM could significantly increase the proportion of DC2.4 maturation ( PP<0.05 or P<0.01), and cell membrane modification had no significant effect on the pro-neovascularization effect of MOF. Conclusion: The synthesized MOF@CCM has good cell compatibility at the dose used and can significantly promote the maturation of DC2.4 cells and HUVEC angiogenesis. It is expected to become a bifunctional treatment platform for anti-colon cancer treatment and tissue repair promotion.
Objective: To explore the potential of colon cancer cell membrane-coated copper-based metal-organic frameworks (MOF@CCM) in anti-tumor activities and promotion of tissue healing. Methods: Copper (Ⅱ) 1, 3, 5-benzenetricarboxylate copperbased metal-organic framework (HKUST-1) was constructed, and coated with colon cancer cell CT26 membrane on its outer layer to obtain MOF@CCM, which was physically characterized. The biocompatibility of MOF@CCM was determined by CCK-8 assay, and the effect of MOF@CCM on the proportion of DC2.4 maturation was analyzed by flow cytometry to verify the potential of MOF@CCM in activating immune cells. Angiogenesis experiments was used to verify the potential of MOF@CCM in promoting HUVEC to form blood vessels. Results: MOF@CCM was successfully synthesized. Transmission electron microscopy showed that its shape was approximately circular and had an obvious core-shell structure. The average particle size of MOF@CCM was (150.5±7.89) nm, and the average Zeta potential was -(5.12±1.67) mV. The results of in vitro experiments showed that compared with the control group, MOF@CCM could significantly increase the proportion of DC2.4 maturation ( PP<0.05 or P<0.01), and cell membrane modification had no significant effect on the pro-neovascularization effect of MOF. Conclusion: The synthesized MOF@CCM has good cell compatibility at the dose used and can significantly promote the maturation of DC2.4 cells and HUVEC angiogenesis. It is expected to become a bifunctional treatment platform for anti-colon cancer treatment and tissue repair promotion.
2024, 31(6):558-565.
DOI: 10.3872/j.issn.1007-385X.2024.06.003
Abstract:
Objective: To investigate the expression, function and possible regulatory mechanisms of transcription factor HOXC13 in laryngeal squamous cell carcinoma (LSCC). Methods: LSCC cells were routinely cultured and divided into sh-NC group, sh-HOXC13 group, pcDNA3.1-NC group, pcDNA3.1-HOXC13 group, pcDNA3.1-PCNA group, and sh-HOXC13+pcDNA3.1-PCNA group, and the corresponding nucleic acids and plasmids were transfected into each group of cells with transfection reagents. GEO Database data were used to analyze the expression of HOXC13 mRNA in LSCC tissues. Sixty-two pairs of LSCC tissues and paired adjacent tissues that were surgically removed in the 980th Hospital of the Joint Logistics Support Force between January 2019 and December 2022 were collected. The expression of HOXC13 protein in Chinese LSCC tissues were detected by immunohistochemistry. The expressions of HOXC13 and PCNA mRNA in Chinese LSCC tissues, adjacent non-cancerous tissues, and various cell lines were detected by qPCR. The proliferation ability of AMC-HN-8 cells in different groups was detected by the MTS method. Plate cloning assay was used to detect the clone formation ability of transfected AMC-HN-8 cells in each group. The migration and invasion abilities of AMC-HN-8 cells in each group were determined by transwell chamber experiments. The binding relationship between HOXC13 and PCNA was verified by dual luciferase reporter gene assays and chromatin immunoprecipitation (ChIP) techniques. Results: HOXC13 and PCNA were highly expressed in LSCC tissues and cells (P<0.05 or P<0.01). Their expression levels were positively correlated (P<0.01), and the expression level of HOXC13 was significantly correlated with TNM stage (P<0.01). Knockdown of HOXC13 significantly inhibited the proliferation, migration and invasion abilities of AMC-HN-8 cells (all P<0.01), and overexpression of HOXC13 promoted the proliferation, migration and invasion abilities of TU686 cancer cells (all P<0.01). HOXC13 could bind to the promoter region of PCNA and regulate its transcription. Knockdown of PCNA partially reversed the promotion of HOXC13 on the malignant biological behaviors of AMC-HN-8 cells (all P<0.01). Conclusion: HOXC13 promotes the malignant biological behaviors of LSCC cells by upregulating PCNA. HOXC13 is a potential target for clinical diagnosis and treatment of LSSC.
Objective: To investigate the expression, function and possible regulatory mechanisms of transcription factor HOXC13 in laryngeal squamous cell carcinoma (LSCC). Methods: LSCC cells were routinely cultured and divided into sh-NC group, sh-HOXC13 group, pcDNA3.1-NC group, pcDNA3.1-HOXC13 group, pcDNA3.1-PCNA group, and sh-HOXC13+pcDNA3.1-PCNA group, and the corresponding nucleic acids and plasmids were transfected into each group of cells with transfection reagents. GEO Database data were used to analyze the expression of HOXC13 mRNA in LSCC tissues. Sixty-two pairs of LSCC tissues and paired adjacent tissues that were surgically removed in the 980th Hospital of the Joint Logistics Support Force between January 2019 and December 2022 were collected. The expression of HOXC13 protein in Chinese LSCC tissues were detected by immunohistochemistry. The expressions of HOXC13 and PCNA mRNA in Chinese LSCC tissues, adjacent non-cancerous tissues, and various cell lines were detected by qPCR. The proliferation ability of AMC-HN-8 cells in different groups was detected by the MTS method. Plate cloning assay was used to detect the clone formation ability of transfected AMC-HN-8 cells in each group. The migration and invasion abilities of AMC-HN-8 cells in each group were determined by transwell chamber experiments. The binding relationship between HOXC13 and PCNA was verified by dual luciferase reporter gene assays and chromatin immunoprecipitation (ChIP) techniques. Results: HOXC13 and PCNA were highly expressed in LSCC tissues and cells (P<0.05 or P<0.01). Their expression levels were positively correlated (P<0.01), and the expression level of HOXC13 was significantly correlated with TNM stage (P<0.01). Knockdown of HOXC13 significantly inhibited the proliferation, migration and invasion abilities of AMC-HN-8 cells (all P<0.01), and overexpression of HOXC13 promoted the proliferation, migration and invasion abilities of TU686 cancer cells (all P<0.01). HOXC13 could bind to the promoter region of PCNA and regulate its transcription. Knockdown of PCNA partially reversed the promotion of HOXC13 on the malignant biological behaviors of AMC-HN-8 cells (all P<0.01). Conclusion: HOXC13 promotes the malignant biological behaviors of LSCC cells by upregulating PCNA. HOXC13 is a potential target for clinical diagnosis and treatment of LSSC.
2024, 31(6):566-572.
DOI: 10.3872/j.issn.1007-385X.2024.06.004
Abstract:
Objective: To investigate the effects of phillyrin (Phi) on the proliferation, migration and invasion of colorectal cancer LS180 cells by regulating the Hippo/YAP signaling pathway. Methods: Human colon cancer LS180 cells were treated with Phi at different concentrations (0, 5, 10, 20, 40, 80 μmol/L), and cell vitality at 24, 48, and 72 h was detected by MTT assay. LS180 cells were divided into the Control group, the Phi-L (5 μmol/L Phi) group, the Phi-M (10 μmol/L Phi) group, the Phi-H (20 μmol/L Phi) group, and the Phi-H+YAP inhibitor verteporfin (VP) group (20 μmol/L Phi+5 μmol/L VP). EdU was applied to detect the effects of Phi on cell proliferation in each group; scratch healing test and Transwell chamber experiments were applied to detect the effects of Phi on cell migration and invasion, respectively; the effects of Phi on Ki-67 expression rate and LATS1, YAP, p-YAP, MMP-2, MMP-9, E-cadherin and N-cadherin expressions were detected by immunofluorescence and WB. A nude mouse model of LS180 cell transplanted tumor was constructed to observe the effects of Phi on the volume and mass of transplanted tumors. Ki-67 expression rate and the expression levels of LATS1, YAP and p-YAP proteins in transplanted tumor tissues were detected by immunofluorescence and WB methods. Results: Compared with the Control group, the cell EdU positive rate, scratch healing rate, cell invasion number, Ki-67 positive rate, MMP-2, MMP-9 and N-cadherin expression levels of LS180 cells in the Phi-L, Phi-M, and Phi-H groups decreased significantly (all P<0.05), while the expression levels of E-cadherin, LATS1 and p-YAP/YAP increased significantly (all P<0.05). The inhibition of Phi on the proliferation, migration and invasion of LS180 cells was partially reversed when VP was used simultaneously. Phi significantly inhibited tumor growth in nude mice. Compared with the Control group, the tumor volume, mass and Ki-67 positive rate of nude mice in the Phi group decreased significantly (all P<0.05), while the levels of LATS1 and p-YAP/YAP increased significantly (all P<0.05). Conclusion: Phi may inhibit the malignant biological behaviors of colon cancer LS180 cells by activating the Hippo/YAP signaling pathway.
Objective: To investigate the effects of phillyrin (Phi) on the proliferation, migration and invasion of colorectal cancer LS180 cells by regulating the Hippo/YAP signaling pathway. Methods: Human colon cancer LS180 cells were treated with Phi at different concentrations (0, 5, 10, 20, 40, 80 μmol/L), and cell vitality at 24, 48, and 72 h was detected by MTT assay. LS180 cells were divided into the Control group, the Phi-L (5 μmol/L Phi) group, the Phi-M (10 μmol/L Phi) group, the Phi-H (20 μmol/L Phi) group, and the Phi-H+YAP inhibitor verteporfin (VP) group (20 μmol/L Phi+5 μmol/L VP). EdU was applied to detect the effects of Phi on cell proliferation in each group; scratch healing test and Transwell chamber experiments were applied to detect the effects of Phi on cell migration and invasion, respectively; the effects of Phi on Ki-67 expression rate and LATS1, YAP, p-YAP, MMP-2, MMP-9, E-cadherin and N-cadherin expressions were detected by immunofluorescence and WB. A nude mouse model of LS180 cell transplanted tumor was constructed to observe the effects of Phi on the volume and mass of transplanted tumors. Ki-67 expression rate and the expression levels of LATS1, YAP and p-YAP proteins in transplanted tumor tissues were detected by immunofluorescence and WB methods. Results: Compared with the Control group, the cell EdU positive rate, scratch healing rate, cell invasion number, Ki-67 positive rate, MMP-2, MMP-9 and N-cadherin expression levels of LS180 cells in the Phi-L, Phi-M, and Phi-H groups decreased significantly (all P<0.05), while the expression levels of E-cadherin, LATS1 and p-YAP/YAP increased significantly (all P<0.05). The inhibition of Phi on the proliferation, migration and invasion of LS180 cells was partially reversed when VP was used simultaneously. Phi significantly inhibited tumor growth in nude mice. Compared with the Control group, the tumor volume, mass and Ki-67 positive rate of nude mice in the Phi group decreased significantly (all P<0.05), while the levels of LATS1 and p-YAP/YAP increased significantly (all P<0.05). Conclusion: Phi may inhibit the malignant biological behaviors of colon cancer LS180 cells by activating the Hippo/YAP signaling pathway.
2024, 31(6):573-578.
DOI: 10.3872/j.issn.1007-385X.2024.06.005
Abstract:
Objective: To investigate the effects of caffeine on the proliferation, migration and invasion abilities of human brain glioma U-373MG cells by regulating the FAK/AKT/ROCK signaling pathway. Methods: U-373MG cells were routinely cultured and divided into the control group, the low dose caffeine (1 mmol/L) group, the high dose caffeine (2 mmol/L) group, the PF573228 group (FAK inhibitor, 1 μmol/L), and the high dose caffeine+SC79 group (AKT activator, 8 mg/L). The proliferation ability, migration ability, invasion ability and apoptosis rate of U-373MG cells in each group as well as the expression levels of p-FAK, p-AKT, p-ROCK, Ki67 and MMP-9 proteins in U-373MG cells were detected by CCK-8, Transwell assay, flow cytometry and WB assay, respectively. A U-373MG cell nude mouse model was established to observe the effect of caffeine on the growth of transplanted tumor. The expressions of related proteins in transplanted tumor tissues were detected by WB method. Results: Caffeine and PF573228 could significantly inhibit the proliferation, migration and invasion abilities of U-373MG cells, promote apoptosis of U-373MG cells, and inhibit the expressions of p-FAK, p-Akt, p-Rock, Ki67 and MMP-9 proteins (all P<0.05). SC79 could partially reverse the effect of caffeine on U-373MG cells. Caffeine could significantly inhibit the growth of transplanted tumors and the expressions of above related proteins in transplanted tumor tissues (all P<0.05). Conclusion: Caffeine can inhibit the proliferation, migration and invasion abilities of U-373MG cells and promote their apoptosis by inhibiting the FAK/AKT/ROCK signaling pathway.
Objective: To investigate the effects of caffeine on the proliferation, migration and invasion abilities of human brain glioma U-373MG cells by regulating the FAK/AKT/ROCK signaling pathway. Methods: U-373MG cells were routinely cultured and divided into the control group, the low dose caffeine (1 mmol/L) group, the high dose caffeine (2 mmol/L) group, the PF573228 group (FAK inhibitor, 1 μmol/L), and the high dose caffeine+SC79 group (AKT activator, 8 mg/L). The proliferation ability, migration ability, invasion ability and apoptosis rate of U-373MG cells in each group as well as the expression levels of p-FAK, p-AKT, p-ROCK, Ki67 and MMP-9 proteins in U-373MG cells were detected by CCK-8, Transwell assay, flow cytometry and WB assay, respectively. A U-373MG cell nude mouse model was established to observe the effect of caffeine on the growth of transplanted tumor. The expressions of related proteins in transplanted tumor tissues were detected by WB method. Results: Caffeine and PF573228 could significantly inhibit the proliferation, migration and invasion abilities of U-373MG cells, promote apoptosis of U-373MG cells, and inhibit the expressions of p-FAK, p-Akt, p-Rock, Ki67 and MMP-9 proteins (all P<0.05). SC79 could partially reverse the effect of caffeine on U-373MG cells. Caffeine could significantly inhibit the growth of transplanted tumors and the expressions of above related proteins in transplanted tumor tissues (all P<0.05). Conclusion: Caffeine can inhibit the proliferation, migration and invasion abilities of U-373MG cells and promote their apoptosis by inhibiting the FAK/AKT/ROCK signaling pathway.
2024, 31(6):579-585.
DOI: 10.3872/j.issn.1007-385X.2024.06.006
Abstract:
Objective: To investigate the mechanism of triptolide (TPL) regulating Notch1 expression on ferroptosis of osteosarcoma U2OS cells via miR-34b-5p. Method: U2OS cells were routinely cultured and divided into the control group , the TPL (10 μmol/L) group, the TPL (10 μmol/L)+Fer-1 (ferroptosis inhibitor, 20 μmol/L) group, the miR-NC, miR-34b-5p, miR-34b-5p+Fer-1 (20 μmol/L) group, the TPL (10 μmol/L)+anti-miR-34b-5p group, and the anti-miR-34b-5p+Fer-1 (20 μmol/L) group. qPCR assay, CCK-8 assay, ferric ion detection reagent, DHE-fluorescent probe, and WB assay were used to detect the expression of miR-34b-5p, the proliferative ability, and the level of Fe2+, ROS levels and the expression of GPX4, SLC7A11 and Notch1 proteins, respectively. Dual luciferase reporter gene assay was used to verify the targeted binding relationship between miR-34b-5p and Notch1. Results: TPL promoted miR-34b-5p expression in U2OS cells, while Fer-1 and anti-miR-34b-5p inhibited miR-34b-5p expression (all P<0.05）. TPL significantly inhibited the proliferation of U2OS cells, the expression of ferroptosis-related proteins (GPX4, SLC7A11, and Notch1 proteins), and increased the cellular Fe2+ and ROS content, and Fer-1 reversed the effect of TPL on U2OS cells (all P<0.05）. Overexpressing miR-34b-5p had similar effects on U2OS cells as TPL (all P<0.05）. miR-34b-5p can be targeted to bind Notch1 (all P<0.05）. miR-34b-5p inhibitor could significantly inhibit the effect of TPL on U2OS cells (all P<0.05）. Fer-1 could enhance the effect of miR-34b-5p inhibitor (all P<0.05）. Conclusion: TPL inhibits the proliferative capacity and promotes ferroptosis of U2OS cells, and its mechanism may be related to the targeted regulation of Notch1 expression by miR-34a-5p.
Objective: To investigate the mechanism of triptolide (TPL) regulating Notch1 expression on ferroptosis of osteosarcoma U2OS cells via miR-34b-5p. Method: U2OS cells were routinely cultured and divided into the control group , the TPL (10 μmol/L) group, the TPL (10 μmol/L)+Fer-1 (ferroptosis inhibitor, 20 μmol/L) group, the miR-NC, miR-34b-5p, miR-34b-5p+Fer-1 (20 μmol/L) group, the TPL (10 μmol/L)+anti-miR-34b-5p group, and the anti-miR-34b-5p+Fer-1 (20 μmol/L) group. qPCR assay, CCK-8 assay, ferric ion detection reagent, DHE-fluorescent probe, and WB assay were used to detect the expression of miR-34b-5p, the proliferative ability, and the level of Fe2+, ROS levels and the expression of GPX4, SLC7A11 and Notch1 proteins, respectively. Dual luciferase reporter gene assay was used to verify the targeted binding relationship between miR-34b-5p and Notch1. Results: TPL promoted miR-34b-5p expression in U2OS cells, while Fer-1 and anti-miR-34b-5p inhibited miR-34b-5p expression (all P<0.05）. TPL significantly inhibited the proliferation of U2OS cells, the expression of ferroptosis-related proteins (GPX4, SLC7A11, and Notch1 proteins), and increased the cellular Fe2+ and ROS content, and Fer-1 reversed the effect of TPL on U2OS cells (all P<0.05）. Overexpressing miR-34b-5p had similar effects on U2OS cells as TPL (all P<0.05）. miR-34b-5p can be targeted to bind Notch1 (all P<0.05）. miR-34b-5p inhibitor could significantly inhibit the effect of TPL on U2OS cells (all P<0.05）. Fer-1 could enhance the effect of miR-34b-5p inhibitor (all P<0.05）. Conclusion: TPL inhibits the proliferative capacity and promotes ferroptosis of U2OS cells, and its mechanism may be related to the targeted regulation of Notch1 expression by miR-34a-5p.
7 SETD5 regulates colon cancer cell migration and 5-FU sensitivity by mediating AKT1 phosphorylation
2024, 31(6):586-591.
DOI: 10.3872/j.issn.1007-385X.2024.06.007
Abstract:
Objective: To investigate the effect of SET domain-containing 5 (SETD5) on the proliferation, migration and 5-fluorouracil (5-FU) drug sensitivity of colon cancer cells and its mechanism. Methods: Colon cancer cells were cultured routinely, and siSETD5-NC and si-SETD5-1-3 plasmids were transfected into HT-29 cells with Lipofectamine 2000. The cells were divided into the control group (untreated), the si-SETD5-NC group, the si-SETD5 group and the si-SETD5+SC79 group. The HT-29 cells in the si-SETD5+SC79 group were transfected with plasmids and treated simultaneously with 10 μmol/L SC79. SETD5 mRNA expression in NCM460, HT-29 and LoVo cells was detected by qPCR. Flow cytometry, cell scratch method, WB method and CCK-8 method were used to detect the apoptosis, migration ability, expression of related proteins and sensitivity to 5-FU of HT-29 cells in each group, respectively. Results: SETD5 mRNA was highly expressed in both HT-29 and LoVo cells (both P<0.01). SETD5 mRNA was successfully knocked down in HT-29 cells (P<0.01). Knockdown of SETD5 mRNA could significantly inhibit the proliferation activity (P<0.01), migration ability (P<0.01), expression of related proteins (SETD5, p-PI3K, p-AKT1, p-mTOR protein) of HT-29 cells (all P<0.01), promote apoptosis (P<0.01), and increase the sensitivity to 5-FU (P<0.01). These effects could be partially blocked by AKT activator SC79 (P<0.05 or P<0.01). Conclusion: SETD5 is highly expressed in HT-29 and LoVo cells. SETD5 promotes the proliferation and migration of colon cancer HT-29 cells and reduces sensitivity to 5-FU through PI3K/AKT1 pathway. SETD5 is a potential target for clinical diagnosis and treatment of colon cancer.
Objective: To investigate the effect of SET domain-containing 5 (SETD5) on the proliferation, migration and 5-fluorouracil (5-FU) drug sensitivity of colon cancer cells and its mechanism. Methods: Colon cancer cells were cultured routinely, and siSETD5-NC and si-SETD5-1-3 plasmids were transfected into HT-29 cells with Lipofectamine 2000. The cells were divided into the control group (untreated), the si-SETD5-NC group, the si-SETD5 group and the si-SETD5+SC79 group. The HT-29 cells in the si-SETD5+SC79 group were transfected with plasmids and treated simultaneously with 10 μmol/L SC79. SETD5 mRNA expression in NCM460, HT-29 and LoVo cells was detected by qPCR. Flow cytometry, cell scratch method, WB method and CCK-8 method were used to detect the apoptosis, migration ability, expression of related proteins and sensitivity to 5-FU of HT-29 cells in each group, respectively. Results: SETD5 mRNA was highly expressed in both HT-29 and LoVo cells (both P<0.01). SETD5 mRNA was successfully knocked down in HT-29 cells (P<0.01). Knockdown of SETD5 mRNA could significantly inhibit the proliferation activity (P<0.01), migration ability (P<0.01), expression of related proteins (SETD5, p-PI3K, p-AKT1, p-mTOR protein) of HT-29 cells (all P<0.01), promote apoptosis (P<0.01), and increase the sensitivity to 5-FU (P<0.01). These effects could be partially blocked by AKT activator SC79 (P<0.05 or P<0.01). Conclusion: SETD5 is highly expressed in HT-29 and LoVo cells. SETD5 promotes the proliferation and migration of colon cancer HT-29 cells and reduces sensitivity to 5-FU through PI3K/AKT1 pathway. SETD5 is a potential target for clinical diagnosis and treatment of colon cancer.
2024, 31(6):592-597.
DOI: 10.3872/j.issn.1007-385X.2024.06.008
Abstract:
Objective: To investigate the mechanism of miR-218-5p regulating the glycolytic process in human non-small cell lung cancer A549 cells by targeting phosphodiesterase 7A (PDE7A). Methods: A549 cells were routinely cultured, and miR-218-5p mimic, mimic-NC, PDE7A overexpression plasmid (PDE7A-oe) and PDE7A control plasmid (PDE7A-NC) were transfected into A549 cells using Lipo3000, and recorded as the miR-218-5p mimic group, the mimic-NC group, the PDE7A-oe group and the PDE7A-NC group. The transfection efficiency was verified by qPCR assay; the expressions of glycolysis key enzyme proteins were detected by WB assay; the 2-deoxyglucose and lactate contents in A549 cells of each transfection group were detected by glucose assay and lactate production assay; the target binding relationship between miR-218-5p and PDE7A was verified by dual-luciferase reporter gene assay, and the data from the TCGA database were used to analyze the expression level of PDE7A mRNA in lung cancer tissues. Results: miR-218-5p was successfully overexpressed in A549 cells (P<0.01). Overexpression of miR-218-5p significantly inhibited the expressions of PDE7A, HK2, PKM2 proteins (all P<0.01), glucose uptake and lactate production (both P<0.01) in A549 cells. Overexpression of PDE7A significantly promoted the expressions of PDE7A, HK2, and PKM2 proteins (all P<0.01), as well as glucose uptake and lactate production (both P<0.01) in A549 cells. miR-218-5p in A549 cells could directly bind to the 3′-UTR of PDE7A mRNA. Database data analysis showed that PDE7A mRNA was highly expressed in lung squamous cell carcinoma tissues (P<0.01). Conclusion: miR-218-5p targets PDE7A to regulate the expression levels of HK2 and PKM2 in A549 cells, which in turn inhibits the glycolytic process. miR-218-5p/PDE7A may be a potential target for clinical diagnosis and treatment of NSCLC.
Objective: To investigate the mechanism of miR-218-5p regulating the glycolytic process in human non-small cell lung cancer A549 cells by targeting phosphodiesterase 7A (PDE7A). Methods: A549 cells were routinely cultured, and miR-218-5p mimic, mimic-NC, PDE7A overexpression plasmid (PDE7A-oe) and PDE7A control plasmid (PDE7A-NC) were transfected into A549 cells using Lipo3000, and recorded as the miR-218-5p mimic group, the mimic-NC group, the PDE7A-oe group and the PDE7A-NC group. The transfection efficiency was verified by qPCR assay; the expressions of glycolysis key enzyme proteins were detected by WB assay; the 2-deoxyglucose and lactate contents in A549 cells of each transfection group were detected by glucose assay and lactate production assay; the target binding relationship between miR-218-5p and PDE7A was verified by dual-luciferase reporter gene assay, and the data from the TCGA database were used to analyze the expression level of PDE7A mRNA in lung cancer tissues. Results: miR-218-5p was successfully overexpressed in A549 cells (P<0.01). Overexpression of miR-218-5p significantly inhibited the expressions of PDE7A, HK2, PKM2 proteins (all P<0.01), glucose uptake and lactate production (both P<0.01) in A549 cells. Overexpression of PDE7A significantly promoted the expressions of PDE7A, HK2, and PKM2 proteins (all P<0.01), as well as glucose uptake and lactate production (both P<0.01) in A549 cells. miR-218-5p in A549 cells could directly bind to the 3′-UTR of PDE7A mRNA. Database data analysis showed that PDE7A mRNA was highly expressed in lung squamous cell carcinoma tissues (P<0.01). Conclusion: miR-218-5p targets PDE7A to regulate the expression levels of HK2 and PKM2 in A549 cells, which in turn inhibits the glycolytic process. miR-218-5p/PDE7A may be a potential target for clinical diagnosis and treatment of NSCLC.
2024, 31(6):598-606.
DOI: 10.3872/j.issn.1007-385X.2024.06.009
Abstract:
Objective: To explore the expression of endocytosis-related gene FCHO2 in different subtypes of breast cancer, and its relationship with the prognosis and immune cell infiltration of breast cancer patients. Methods: Immunohistochemical staining and bc-GenExMiner v5.0 database were used to analyze the expression of FCHO2 in different subtypes of breast cancer. The relationship between FCHO2 and the prognosis and immune cell infiltration of different subtypes of breast cancer patients was analyzed using GEO and TIMER database. The protein-protein interaction network of FCHO2 and its correlation with the interacting proteins were analyzed using STRING database and GEPIA database, respectively. KEGG and GO analysis of FCHO2-related genes in breast cancer tissues were performed using UALCAN and DAVID databases. Results： Immunohistochemical staining showed that FCHO2 in luminal and HER2+ breast cancer tissues were highly expressed (both P<0.05), and correlated with the expressions of HER2 and Ki67 (P=0.03 or P=0.007). Both the OS and RFS of luminal breast cancer patients with high expression of FCHO2 were significantly decreased (both P<0.05). FCHO2 protein was related to the expressions of many proteins such as EPS15 and constituted the protein-protein interaction network. KEGG and GO analysis indicated that the expression of FCHO2-related genes in breast cancer tissues were mainly related to biological processes such as circadian rhythm and autophagy, and involved FoxO and TGF-β signaling pathways. The expression of FCHO2 was correlated with immune cell infiltration in tissues of different subtypes of breast cancer. Conclusion: FCHO2 is highly expressed in luminal and HER2+ breast cancer tissues, and is correlated with the patient prognosis and immune cell infiltration of luminal breast cancer. FCHO2 may become a potential target for breast cancer treatment.
Objective: To explore the expression of endocytosis-related gene FCHO2 in different subtypes of breast cancer, and its relationship with the prognosis and immune cell infiltration of breast cancer patients. Methods: Immunohistochemical staining and bc-GenExMiner v5.0 database were used to analyze the expression of FCHO2 in different subtypes of breast cancer. The relationship between FCHO2 and the prognosis and immune cell infiltration of different subtypes of breast cancer patients was analyzed using GEO and TIMER database. The protein-protein interaction network of FCHO2 and its correlation with the interacting proteins were analyzed using STRING database and GEPIA database, respectively. KEGG and GO analysis of FCHO2-related genes in breast cancer tissues were performed using UALCAN and DAVID databases. Results： Immunohistochemical staining showed that FCHO2 in luminal and HER2+ breast cancer tissues were highly expressed (both P<0.05), and correlated with the expressions of HER2 and Ki67 (P=0.03 or P=0.007). Both the OS and RFS of luminal breast cancer patients with high expression of FCHO2 were significantly decreased (both P<0.05). FCHO2 protein was related to the expressions of many proteins such as EPS15 and constituted the protein-protein interaction network. KEGG and GO analysis indicated that the expression of FCHO2-related genes in breast cancer tissues were mainly related to biological processes such as circadian rhythm and autophagy, and involved FoxO and TGF-β signaling pathways. The expression of FCHO2 was correlated with immune cell infiltration in tissues of different subtypes of breast cancer. Conclusion: FCHO2 is highly expressed in luminal and HER2+ breast cancer tissues, and is correlated with the patient prognosis and immune cell infiltration of luminal breast cancer. FCHO2 may become a potential target for breast cancer treatment.
2024, 31(6):607-612.
DOI: 10.3872/j.issn.1007-385X.2024.06.010
Abstract:
Objective: To investigate whether there are differences in immunological indicators between multiple myeloma (MM) patients with renal impairment (RI) and those without. Methods: A retrospective analysis was conducted on 134 patients who were admitted to the Second Hospital of Lanzhou University and first diagnosed with MM from January 2017 to August 2023. The study compared the differences in 10 immunological indicators and 6 routine hematological parameters between the RI group and the non-RI group, as well as the Durie?Salmon (DS) staging and risk stratification subgroups. Results: The peripheral blood neutrophil/lymphocyte ratio (NLR), peripheral blood monocyte/lymphocyte ratio (MLR), CD8+ T cell ratio, and IL-10 in the RI group were all higher than those in the non-RI group (all P<0.05), while the absolute value of lymphocytes and CD4/CD8 ratio were both lower than those in the non-RI group (both P<0.05). In DS-Ⅲ stage patients, the proportion of NLR, MLR, CD8+ T cells, IL-8, and IL-10 in the RI group were all higher than those in the non-RI group (all P<0.05). However, there was no significant difference in immune indicators between the RI and non-RI groups in DS-Ⅰ and DS-Ⅱ patients. The number of lymphocytes, NLR, and IL-10 in the RI group of high-risk MM patients showed significant differences compared to those in non-RI patients (all P<0.05). Conclusion: Immunological abnormalities are more pronounced in MM patients with RI, and significant immune abnormalities are observed in DS-Ⅲ staging and high-risk stratification. The results of this study provide a reference for further elucidating the reasons for poor prognosis in MM patients with RI and personalized treatment.
Objective: To investigate whether there are differences in immunological indicators between multiple myeloma (MM) patients with renal impairment (RI) and those without. Methods: A retrospective analysis was conducted on 134 patients who were admitted to the Second Hospital of Lanzhou University and first diagnosed with MM from January 2017 to August 2023. The study compared the differences in 10 immunological indicators and 6 routine hematological parameters between the RI group and the non-RI group, as well as the Durie?Salmon (DS) staging and risk stratification subgroups. Results: The peripheral blood neutrophil/lymphocyte ratio (NLR), peripheral blood monocyte/lymphocyte ratio (MLR), CD8+ T cell ratio, and IL-10 in the RI group were all higher than those in the non-RI group (all P<0.05), while the absolute value of lymphocytes and CD4/CD8 ratio were both lower than those in the non-RI group (both P<0.05). In DS-Ⅲ stage patients, the proportion of NLR, MLR, CD8+ T cells, IL-8, and IL-10 in the RI group were all higher than those in the non-RI group (all P<0.05). However, there was no significant difference in immune indicators between the RI and non-RI groups in DS-Ⅰ and DS-Ⅱ patients. The number of lymphocytes, NLR, and IL-10 in the RI group of high-risk MM patients showed significant differences compared to those in non-RI patients (all P<0.05). Conclusion: Immunological abnormalities are more pronounced in MM patients with RI, and significant immune abnormalities are observed in DS-Ⅲ staging and high-risk stratification. The results of this study provide a reference for further elucidating the reasons for poor prognosis in MM patients with RI and personalized treatment.
2024, 31(6):613-620.
DOI: 10.3872/j.issn.1007-385X.2024.06.011
Abstract:
神经胶质瘤是人中枢神经系统最常见的原发性恶性肿瘤，肿瘤呈浸润性生长，难以彻底切除，且患者易出现放化疗耐 药，复发率和病死率均较高，预后较差。近年来，免疫疗法的有效性在多种肿瘤中得到证实。目前，胶质母细胞瘤（GBM）的免疫 疗法主要包括CAR-T细胞治疗、溶瘤病毒治疗、疫苗接种和免疫检查点抑制剂治疗等。这标志着新兴的免疫疗法在神经胶质瘤 治疗领域取得了显著进步。但仍然存在一些问题限制了免疫疗法的进一步应用，如给药途径存在障碍等问题，同时，科研工作者 们也给出了相应的对策，如免疫疗法与纳米生物相结合扩宽给药途径等。为此，本文就免疫疗法在神经胶质瘤中发挥的作用及 其治疗效果的相关进展进行了介绍，并总结了当前免疫治疗存在的问题及解决对策，为临床治疗神经胶质瘤提供参考。
神经胶质瘤是人中枢神经系统最常见的原发性恶性肿瘤，肿瘤呈浸润性生长，难以彻底切除，且患者易出现放化疗耐 药，复发率和病死率均较高，预后较差。近年来，免疫疗法的有效性在多种肿瘤中得到证实。目前，胶质母细胞瘤（GBM）的免疫 疗法主要包括CAR-T细胞治疗、溶瘤病毒治疗、疫苗接种和免疫检查点抑制剂治疗等。这标志着新兴的免疫疗法在神经胶质瘤 治疗领域取得了显著进步。但仍然存在一些问题限制了免疫疗法的进一步应用，如给药途径存在障碍等问题，同时，科研工作者 们也给出了相应的对策，如免疫疗法与纳米生物相结合扩宽给药途径等。为此，本文就免疫疗法在神经胶质瘤中发挥的作用及 其治疗效果的相关进展进行了介绍，并总结了当前免疫治疗存在的问题及解决对策，为临床治疗神经胶质瘤提供参考。
2024, 31(6):621-625.
DOI: 10.3872/j.issn.1007-385X.2024.06.012
Abstract:
血管生成拟态（VM）是一种独立于内皮细胞的血管样结构，通常存在于需要血管生长的实体肿瘤中。VM与肿瘤细 胞的增殖、侵袭、转移及胃癌患者的不良预后密切相关。VM的存在可能是胃癌患者抗血管生成药物耐药的原因之一，抗血管生 成同时靶向VM治疗将有望成为胃癌治疗的新方向。
血管生成拟态（VM）是一种独立于内皮细胞的血管样结构，通常存在于需要血管生长的实体肿瘤中。VM与肿瘤细 胞的增殖、侵袭、转移及胃癌患者的不良预后密切相关。VM的存在可能是胃癌患者抗血管生成药物耐药的原因之一，抗血管生 成同时靶向VM治疗将有望成为胃癌治疗的新方向。
2024, 31(6):626-631.
DOI: 10.3872/j.issn.1007-385X.2024.06.013
Abstract:
基于纳米粒子的光疗主要包括光动力疗法（PDT）和光热疗法（PTT）。近年来，光疗联合免疫检查点抑制剂（ICI）的疗 法显示出治疗恶性肿瘤的巨大潜力。这种联合疗法结合了抗体介导的靶向给药和激光激活的一系列生物/物理机制，能准确诱导 癌细胞快速死亡，同时避免损伤周围正常组织，ICI与光疗联合应用能产生协同效应，从而提高治疗效果，减少肿瘤复发和转移。 目前，这种联合疗法已在临床前研究中显示出潜力，可用于大部分常见的恶性肿瘤，如肺癌、乳腺癌、食管癌等的治疗，但面临着 激光穿透不足、不良反应等问题。未来研究需要优化治疗方案，提高其安全性和有效性。
基于纳米粒子的光疗主要包括光动力疗法（PDT）和光热疗法（PTT）。近年来，光疗联合免疫检查点抑制剂（ICI）的疗 法显示出治疗恶性肿瘤的巨大潜力。这种联合疗法结合了抗体介导的靶向给药和激光激活的一系列生物/物理机制，能准确诱导 癌细胞快速死亡，同时避免损伤周围正常组织，ICI与光疗联合应用能产生协同效应，从而提高治疗效果，减少肿瘤复发和转移。 目前，这种联合疗法已在临床前研究中显示出潜力，可用于大部分常见的恶性肿瘤，如肺癌、乳腺癌、食管癌等的治疗，但面临着 激光穿透不足、不良反应等问题。未来研究需要优化治疗方案，提高其安全性和有效性。
2024, 31(6):632-638.
DOI: 10.3872/j.issn.1007-385X.2024.06.014
Abstract:
小细胞肺癌（SCLC）的治疗已经迈入免疫治疗时代，免疫疗法联合化疗的一线治疗新标准得以确立。然而并非所有 SCLC患者均能从免疫检查点抑制剂（ICI）中获益，缺乏有效的疗效和患者预后生物标志物在很大程度上限制了其临床应用。目 前，肿瘤相关生物标志物PD-L1表达水平在预测SCLC免疫治疗疗效及患者预后中最为常用；肿瘤突变负荷（TMB）、错配修复缺 陷（dMMR） 和微卫星高度不稳定（MSI-H）也可作为预测 ICI 治疗疗效及患者预后的潜在生物标志物。而 dMMR/MSI-H 因在 SCLC中的发生频率极低，限制了其应用；外周血免疫相关标志物因其便捷性而在SCLC免疫治疗中受到越来越多的关注；肿瘤 微环境相关的生物标志物也有助于识别从ICI治疗中获益的患者。因此，深入了解SCLC的一线免疫治疗现状和预测患者免疫 治疗疗效与预后的潜在生物标志物的研究进展，可为SCLC患者免疫治疗优化策略和分层管理提供思路和参考。
小细胞肺癌（SCLC）的治疗已经迈入免疫治疗时代，免疫疗法联合化疗的一线治疗新标准得以确立。然而并非所有 SCLC患者均能从免疫检查点抑制剂（ICI）中获益，缺乏有效的疗效和患者预后生物标志物在很大程度上限制了其临床应用。目 前，肿瘤相关生物标志物PD-L1表达水平在预测SCLC免疫治疗疗效及患者预后中最为常用；肿瘤突变负荷（TMB）、错配修复缺 陷（dMMR） 和微卫星高度不稳定（MSI-H）也可作为预测 ICI 治疗疗效及患者预后的潜在生物标志物。而 dMMR/MSI-H 因在 SCLC中的发生频率极低，限制了其应用；外周血免疫相关标志物因其便捷性而在SCLC免疫治疗中受到越来越多的关注；肿瘤 微环境相关的生物标志物也有助于识别从ICI治疗中获益的患者。因此，深入了解SCLC的一线免疫治疗现状和预测患者免疫 治疗疗效与预后的潜在生物标志物的研究进展，可为SCLC患者免疫治疗优化策略和分层管理提供思路和参考。
2024, 31(6):639-643.
DOI: 10.3872/j.issn.1007-385X.2024.06.015
Abstract:
人表皮生长因子受体2（HER2）过表达与肿瘤的侵袭性和患者预后不良有关。HER2靶向药物的出现改善了HER2阳 性转移性乳腺癌（MBC）的临床结局，甚至一些患者可能达到长期生存。目前，长期缓解的原因未明，曲妥珠单抗联合帕妥珠单抗 停药后复发风险的证据有限。本文报告1例HER2扩增的MBC患者，经过6个周期帕妥珠单抗+曲妥珠单抗联合化疗后达到临床 部分缓解（cPR）。后患者行右乳腺癌改良根治术，术后病理检测结果显示病理完全缓解（pCR）。术后先后使用化疗联合靶向治 疗、内分泌治疗（ET）联合靶向治疗。截至目前，尚无疾病进展的临床证据。该例治疗模式为 MBC 患者的治疗提供了有益的 帮助。
人表皮生长因子受体2（HER2）过表达与肿瘤的侵袭性和患者预后不良有关。HER2靶向药物的出现改善了HER2阳 性转移性乳腺癌（MBC）的临床结局，甚至一些患者可能达到长期生存。目前，长期缓解的原因未明，曲妥珠单抗联合帕妥珠单抗 停药后复发风险的证据有限。本文报告1例HER2扩增的MBC患者，经过6个周期帕妥珠单抗+曲妥珠单抗联合化疗后达到临床 部分缓解（cPR）。后患者行右乳腺癌改良根治术，术后病理检测结果显示病理完全缓解（pCR）。术后先后使用化疗联合靶向治 疗、内分泌治疗（ET）联合靶向治疗。截至目前，尚无疾病进展的临床证据。该例治疗模式为 MBC 患者的治疗提供了有益的 帮助。
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- 《中国肿瘤生物治疗杂志》
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- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
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- 刊号：ISSN 1007-385X
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.