Potentiation of Cisplatin Activity in Colorectal Cancer Cells by Lovastatin

Abstract

Cisplatin (CIS) is an anticancer drugs used in the treatment of several solid tumors with nephrotoxicity as its main toxic effect. The current study was directed to assess the role of hypolipidemic drug (lovastatin) on sensitization of human colorectal cancer cells (HCT -116) to the action of CIS. This study assessed the action of lovastatin on sensitization of colorectal cancer cells to cisplatin by examining cisplatin cytotoxicity, cisplatin cellular uptake and P-glycoprotein (P-gp) activity in presence and absence of Lovastatin 10 and 30 ug/ml. Lovastatin treatment at dose level of 10 and 30 µg/ml potentiated the cytocidal effect of cisplatin against the growth of HCT-116 cells with IC50 7.3 and 5.4 µg/ml, respectively compare to 18 µg/ml after treatment with cisplatin alone. Moreover, lovastatin increased the uptake of cisplatin into colorectal cancer cells with marked inhibition of P-glycoprotein pump. On conclusion Lovastatin treatment increases the antiproliferative activity of cisplatin against the growth of colorectal cancer cells due to inhibition the activity P-glycoprotein pump with marked increase in its cellular uptake.