Inhibition of VEGFA Increases the Sensitivity of Ovarian Cancer Cells to Chemotherapy by Suppressing VEGFA-Mediated Autophagy

摘要

Background: Ovarian cancer (OvCa) is the leading cause of death of gynecological malignancies worldwide. Vascular endothelial growth factor A (VEGFA), the most potent angiogenic factor, is responsible for tumor growth and angiogenesis, but its role in OvCa chemotherapy resistance remains unclear. Methods: RT-PCR and Western blot were used to detect VEGFA expression in tumor cells and normal ovarian surface epithelial cells. Gene Ontology (GO) enrichment analysis was used to analyze GO terms correlated with VEGFA. In in vitro experiments, we knockdown VEGFA in tumor cells and detected the tumor cell viability and apoptosis after chemotherapy drug treatment by MTT assay and flow cytometry. Western blot was used to detect autophagy and apoptosis related proteins. Results: We proved that VEGFA was highly expressed in tumor cells comparted with normal ovarian surface epithelial cells, and enriched GO analysis of VEGFA showed that VEGFA was involved in anti-apoptotic process. Further in vitro experiments confirmed that expression of VEGFA was correlated with chemotherapy resistance and this effect was mediated by autophagy. Meanwhile tumor cells treated with chemotherapy drugs also promoted the expression of VEGFA. Knockdown VEGFA inhibited autophagy of tumor cells and thus potents the killing efficiency in DDP resistant tumor cells and this effect could be reversed by the addition of recombinant VEGFA. Conclusion: Taken together, our study demonstrates that VEGFA is involved in anti-apoptosis of tumor cells to chemotherapy, killing partly through autophagy, indicating that VEGFA may serve as a potential target to improve chemotherapy treatment.