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P‐glycoprotein expression induced by glucose depletion enhanced the chemosensitivity in human hepatocellular carcinoma cell‐lines
Author(s) -
Cheng Samuel ChakSum,
Zhou Jing,
Xie Yong
Publication year - 2005
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2004.12.010
Subject(s) - p glycoprotein , cell culture , cancer cell , in vitro , cytotoxicity , verapamil , cancer research , cell , telomerase , drug resistance , microbiology and biotechnology , biology , chemistry , pharmacology , multiple drug resistance , cancer , gene , biochemistry , medicine , genetics , calcium
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.