P-glycoprotein expression induced by glucose depletion enhanced the chemosensitivity in human hepatocellular
Samuel Chak-Sum Cheng1, Jing Zhou, Yong Xie
1Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Abstract:
Chemoresistance in cancer cells is frequently associated with an over-expression of the P-glycoprotein (P-gp). The expression of P-gp can be regulated as the cells encounter a number of chemical, physical or environmental stimuli. In this study, P-gp was found gradually expressed in a human hepatocellular carcinoma (HCC) QGY-7703 cells after 48 h of culturing in glucose-free medium. This phenomenon disappeared after the removal of glucose deprivation culture conditions. Mdr1-cDNA isolated from the cell line cultured in glucose-free conditions (namely QGY-7703G), was transiently transformed into the parent QGY-7703 cells, and multi-drug resistance was eventually induced. Results from XTT cytotoxicity assays indicated that the mdr1 gene was functional and the P-gp could restore the QGY-7703 cell's ability to withstand high concentrations of a number of chemotherapeutic agents. A P-gp inhibitor, verapamil, could completely reverse the cellular drug resistance when applied to the QGY-7703G cells. Our results indicated that an alteration of a specific state in cells caused by an external stimulus in vitro may lead to an expression of stress proteins (e.g. P-gp), which may enhance the cells' survival in adverse conditions. The expressed P-gp induced by glucose deprivation has a functional role in affecting the chemosensitivity in HCC QGY-7703G cells. Inhibition of P-gp activity may enhance the effect of the cancer cells towards cancer chemotherapy.