Effect of endogenous multidrug resistance 1 and P‐glycoprotein expression on anticancer drug resistance in colon cancer cell lines

다국어 초록 (Multilingual Abstract)

P‐glycoprotein (P‐gp, multidrug resistance 1 (MDR1)) overexpression confers multidrug resistance to cancer cells, and P‐gp in cell lines transfected with MDR1 or selected with chemotherapeutics significantly affect the anticancer drug efficacy. Although human cancer cell line panels consisting of defined tumor cell lines expressing endogenous P‐gp have been used to screen drugs in pharmaceutical industries, endogenous P‐gp affecting in vitro anticancer drug efficacy is unclear. The impact of P‐gp expression on anticancer drug efficacy was assessed by using five colon cancer cell lines expressing varying endogenous P‐gp levels and by selecting from the Cancer Cell Line Encyclopedia (CCLE). mRNA expression of MDR1 was considered as a surrogate of the protein expression of its gene product, P‐gp, in CL‐11, C2BBe1 and RKO cells, whereas P‐gp protein expression in plasma membranes or crude membrane fractions was lower than expected from mRNA expression in CW‐2 and CL‐40 cells. The EC50 of paclitaxel and vinorelbine decreased in the presence of a P‐gp inhibitor in CW‐2 and CL‐11 cells that highly express P‐gp. No significant alterations in EC50 were observed in the CL‐40, C2BBe1 and RKO cells, which show lower P‐gp expression. Accordingly, the apparent in vitro efficacy of anticancer drugs could be underestimated if the endogenous P‐gp expression is higher than in CL‐11 cells. The effect of P‐gp needs to be carefully evaluated in cell lines that highly express P‐gp, which account for 1.5% of cancer cell lines, including all cancer types, and 14.5% of colon cancer cell lines in CCLE, considering the protein expression levels in plasma membranes.