Succinic Acid-Sunitinib Combination Treatment Downregulates the Angiogenic Gene Expressions in Sunitinib- Resistant Renal Cancer Cell Line.

Drug resistance hinders treatment success in many cancers. Sunitinib is one of the first-line treatments in renal cell carcinoma (RCC), but resistance develops during treatment. By ameliorating their angiogenic ability, tumor cells finding a different route of escape in RCC is a majorconcern. We aimed to investigate the effects of the succinic acid sunitinib combination on the angiogenesis mechanism in sunitinib-resistant renal cancer cell lines. Gene expression levels of VEGF-A, VEGF-C, PDGF-A, HIF1A, TGF-β, VHL, ANGPT1, and TIE2; protein levels of VEGF-A, HIF1A, and VHL were compared before, and after succinic acid-sunitinib combination treatment in ACHN cells that developed sunitinib resistance. In the sunitinib-resistant group, HIF1A, TGF-β, ANGPT1, and TIE2 gene expression levels were significantly decreased with a combination therapy of succinic acid at 25 µMcompared to the resistant control group. Our study focused on clarifying the increase of angiogenic factors in sunitinib-resistant RCC cells following sunitinib treatment and the subsequent changes in the combination of succinic acid as a secondary treatment agent. It is also anticipated to guide future studies exploring the potential clinical application of the combination of sunitinib and succinic acid.