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Archive > Volume 31 Issue 5 > 2024,31(5):452-461. DOI:10.3872/j.issn.1007-385X.2024.05.004 Prev Next
Basic Research
Effects of vesicular stomatitis virus on anti-tumour immunity, growth of xenografts,and lung metastasis in mouse mammary carcinoma 4T1 cells tumor-bearing mice
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Abstract:
Objective: To investigate the effects of wild-type vesicular stomatitis virus strain (VSV-IN ) on immunomodulation and tumour metastasis in mouse triple negative breast cancer (TNBC) 4T1 cell transplantation model mice. Methods: After VSV-IN infected 4T1 cells with MOI=1, MOI=10 and MOI=100 for 12, 24 and 48 h, 4T1 cell mortality was detected by CCK-8 method, migration ability by scratch healing assay, and the expressions of E-cadherin, MMP-2 and MMP-9 mRNA by qPCR. The fat pads of female BALB/c mice were inoculated with 0.1 mL of 4T1 cells with a cell density of 1×106 cells/mL to construct a 4T1 cell-loaded mouse model. When the tumour volume reached 200 mm3, the mice were injected intratumorally with PBS, taxol (TAX) (15 mg/kg), and VSV (1×106 pfu) once a week, respectively. After 4 administrations, mice were executed, stripped of intact grafted tumour tissues, and tumour volume and mass were measured. Histopathological sections of the lungs were stained with H-E, and tumour metastatic nodules of the lungs were observed. The proportion of T-cell subpopulations in the spleen was detected by flow cytometry.The levels of serum IL-6 and TNF-α were detected by ELISA. The expression levels of migration-related proteins in mammary gland tumours were analysed by using the online analysis of GEPIA. The expressions of MMP-2, MMP-9 and E-cadherin in mouse tumours were detected by immunohistochemistry, and the affinity of G and M proteins of VSV-IN and ERK2 and E-cadherin was predicted by protein-protein docking technology. Results: The mortality rate of 4T1 cells after 48 hours of VSV treatment at MOI=10 and 100 were significantly higher than that of the control group (P<0.01). Compared with that of the control group, the cell migration rate of the VSV-IN group (MOI=10) was significantly lower (P<0.01), and the relative expression of MMP-9 mRNA was significantly lower (P<0.05).Compared with those in the mice of the control group, transplanted tumours in the mice of the VSV-IN group grew more slowly, and their endpoint volume was significantly reduced (P<0.05). The number of lung metastatic nodules in the mice of the VSV group was significantly less than that of the control group ([12.86±1.86] vs [24±3.67], P<0.01). The proportions of splenic CD4+ T and CD8+ T cells in the VSV group were significantly higher (both P<0.05). The serum TNF-α and IL-6 levels were significantly higher (both P<0.01). GEPIA tool analysis revealed that the expression levels of E-cadherin and MMP-9 were higher in breast cancer tissues than in paracancerous tissues (P<0.05). The expression of MMP-9 in the tumour cells of the mice in the VSV-IN group was significantly lower than that in the control group (P<0.05). The binding free energies of G and M proteins of VSV-IN to ERK2 were -11.7 kcal/mol and -6.4 kcal/mol, respectively. Conclusion: Wild-type VSV-IN inhibits the growth and metastasis of transplanted tumours in 4T1 tumor-bearing mice, which may be related to its promotion of anti-tumour immunity and modulation of the expression of migration-related proteins.
Keywords:
wild-type vesicular stomatitis virus Indiana strain (wild-type VSV-IN) ; triple negative breast cancer (TNBC) ; 4T1 cell ; migration ; protein-protein docking
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李玉迁,徐庆胜,魏洪,王皞,王硕石,蒋立娜,袁心怡.水疱性口炎病毒对小鼠乳腺癌4T1 细胞荷瘤小鼠抗肿瘤免疫、移植瘤生长与肺转移的影响[J].中国肿瘤生物治疗杂志,2024,31(5):452~461
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History
Manuscript received: December 16,2023
Manuscript revised: April 09,2024
Online Published: June 12,2024