P-glycoprotein expression induced by glucose depletion enhanced the chemosensitivity in human hepatocellular carcinoma cell-lines.
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.
Cheng
Samuel Chak-Sum
SC
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Zhou
Jing
J
Xie
Yong
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D003470:Culture Media; D003609:Dactinomycin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D017239:Paclitaxel / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003470:Culture Media; D003609:Dactinomycin; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D005947:Glucose; D017239:Paclitaxel; D005472:Fluorouracil