Resveratrol enhances chemosensitivity of renal cell carcinoma to paclitaxel.

ABSTRACT

By restraining proliferation and promoting apoptosis, resveratrol (RES) has anti-tumor effect in various cancers. Here, we examine whether RES exerts similar effect in drug-resistant renal cell carcinoma (RCC). To this end, Caki-1 cells derived from renal carcinoma are subjected to escalated doses of paclitaxel (PTX) to produce the PTX resistant Caki-1PTX cells. Both Caki-1 and Caki-PTX cells are sensitive to PTX, in a dose dependent manner. RES, dose-dependently, suppresses the expression of survivin, a molecular biomarker of cancer and a member of the inhibitor of apoptosis (IAP) family and its co-administration with PTX inhibits the effect of this drug on cell viability. To decipher whether survivin expressed by cancer cells is involved in rendering cells PTX sensitive, survivin is overexpressed. This dramatically counteracts the effects of RES on cell survival in the presence of PTX. Furthermore, decrease of survivin by inhibition of PI3K/AKT pathway significantly inhibits the effect of PTX in Caki-1PTX cells. These data show that RES increases the sensitivity of PTX resistant renal cells to drug treatment.