AB014. Sunitinib affects autophagy and apoptosis via regulation of glycolysis in renal cell carcinoma cells

Background: Renal cell carcinoma (RCC) is resistant to regular chemotherapy and radiation. Sunitinib, which targeted to VEGF receptor and other signal pathways, has been proved effective for prolonged cancer specific survival and overall survival for metastatic RCC. There is no report on autophagy induced by sunitinib in RCC cells yet.

Methods: On the other hand, the majority of sporadic RCC have vHL mutations and HIF expression disorder, as HIF is one of the key glycolysis regulatory proteins. But little is known about the relationship between glycolysis and autophagy in RCC cells.

Results: (I) Sunitinib could reduce renal cancer cells proliferation and cause apoptosis; (II) sunitinib induced autophagy flow upregulated while the apoptosis and autophagy were proved related; (III) sunitinib could decrease the expression of glycolysis related genes; (IV) Akt/mTOR pathway played important role in the sunitinib induced autophagy; (V) there were multiple glycolysis related gene upregulated in kidney cancer tissue by microarray test; (VI) sunitinib could induce glycolysis related gene down-regulated; (VII) on the contrary, by regulating the glycolysis, autophagy and apoptosis induced by sunitinib could be significantly influenced.

Conclusions: It suggests that sunitinib may inhibit the process of glycolysis, further induced autophagy and apoptosis.

Keywords: Autophagy; apoptosis; renal cell carcinoma (RCC)