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Archive > Volume 31 Issue 2 > 2024,31(2):154-160. DOI:10.3872/j.issn.1007-385X.2024.02.006 Prev Next
Basic Research
Andrographolide reduces cisplatin resistance of endometrial cancer Ishikawa/DPP cells by inhibiting the Fas/FasL signaling axis
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Abstract:
Objective: To investigate the effect of andrographolide (Andro) regulation of fatty acid synthase (Fas)/fatty acid synthase ligand (FasL) signaling axis on drug resistance of endometrial cancer Ishikawa cells. Methods: Ishikawa cells and cisplatin-resistant Ishikawa/DPP cells were treated respectively with 0, 5, 10 and 20 μg/mL DDP, and Ishikawa/DDP cells were treated with 0, 5, 10, 25 and 50 μmol/L Andro. Cell proliferation was detected by MTT and the appropriate dose of administration was selected for subsequent experiments. Ishikawa/DDP cells were randomly divided into the control group, the DDP group (intervention with DDP), the Andro group (intervention with DDP and Andro), the pcDNA3.1-NC group (transfection with pcDNA3.1 and intervention with DDP and Andro), and the pcDNA3.1-Fas/FasL group (transfection with pcDNA3.1-Fas/FasL and intervention with DDP and Andro). After 24 h of treatment, qPCR was used to detect the mRNA expression of Fas and FasL. Plate cloning assay; Transwell assay and flow cytometry were used to detect cell cloning ability, cell migration, invasion and apoptosis, respectively. The expressions of proliferating cell nuclear antigen (PCNA), BAX, Bcl-2, MMP-2, PD-L1, multidrug resistance protein-1 (MDR-1) and Fas and FasL proteins were detected by WB method. Results: DDP inhibited the proliferation of Ishikawa and Ishikawa/DPP cells in a dose-dependent manner. In addition, the sensitivity of Ishikawa/DPP cells to DDP was lower than that of Ishikawa cells (all P<0.05). Andro inhibited the proliferation of Ishikawa/DPP cells in a dose-dependent manner (all P<0.05). The expression levels of Fas and FasL in Ishikawa/DPP cells were higher than those in Ishikawa cells (all P<0.05). 20 μg/mL DDP and 25 μmol/L Andro were selected as the intervention doses, and the intervention time was 24 h. Compared with the control group, the mRNA and protein expression levels of PD-L1, MDR-1, Fas, FasL in Ishikawa/DPP cells in the DDP group increased significantly (P<0.05), but there were no significant differences in clone formation rate, number of migrating and invading cells and apoptosis rate (all P>0.05). Compared with the DDP group, the mRNA expression levels of Fas and FasL, the cell clone formation rate, the number of migrating and invading cells, the expression levl of PCNA, Bcl-2, MMP-2, PD-L1, MDR-1, Fas and FasL protein decreased significantly, while the expression level of BAX protein and the apoptosis rate increased significantly (P<0.05 or P<0.01). The pcDNA3.1-NC group was similar to the Andro group. Compared with the pcDNA3.1-NC group, the changes of Ishikawa/DPP cells in the pcDNA3.1-Fas/FasL group were reversed (P<0.05). Conclusion: Andro may inhibit the proliferation, migration and invasion of Ishikawa/DPP cells by inhibiting the Fas/FasL signaling axis, promote the apoptosis, and thereby reduce the resistance of cells to DDP.
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