Targeting Renal Cell Carcinoma with Gambogic Acid in Combination with Sunitinib in Vitro and in Vivo

Purpose: To evaluated the effect of the gambogic acid (GA), one of the effective components of Garcinia, incombination with a new multi-targeted oral medication, sunitinib (SU) on renal cancer cell proliferation in vitroand on tumor growth in vivo.
Methods: After treatment with GA or SU, either alone or in combination, MTTand FACS analysis were used to examine cell viability and cycle distribution of the renal carcinoma cell lines786-0 and Caki-1. Western blotting was employed to examine the expression of proteins related to the cell cycleand vascular formation. Furthermore, a xenograft model was applied to study the antitumor efficacy of SU orGA alone or in combination, with immunohistochemistry to detect expression of proteins related to xenograftgrowth and angiogenesis. Western blotting was used to examine NF-κB signaling pathway elements in xenografts.
Results: Treatment of 786-0 and Caki-1 cells with GA or SU resulted in decreased tumor cell proliferation,especially with joint use. Cells accumulated more strongly in the sub-G1 phase after joint treatment with GA andSU than treatment of GA and SU alone. Western blotting arrays showed 1 protein significantly upregulated, 2proteins downregulated, and 2 proteins unchanged. Moreover, combined use of GA and SU inhibited the growthand angiogenesis of xenografts generated from Caki-1 significantly. Immunohistochemistry arrays showeddownregulation of the expression of proteins promoting xenograft growth and angiogenesis, and Western blottingshowed inhibition of the NF-κB signaling pathway after treatment by GA alone and in combination with SUin xenografts.
Conclusions: Our results show that the joint use of GA and SU can provide greater antitumorefficacy compared to either drug alone and thus may offer a new treatment strategy for renal cell carcinoma.