Characterization of a taxol-resistant hepatocellular carcinoma cell line (QGY-TR 50)

Abstract

Cancer chemotherapy with taxol often fails due to acquired resistance of cancer cells, which is frequently associated with an overexpression of P-glycoprotein and alterations of ß-tubulin. A taxol-resistant cell line, QGY-TR50, derived from a human hepatocellular carcinoma (HCC) QGY-7703 cell line was used to investigate the mechanisms of taxol-resistance. QGY-TR50 cells showed more than 250-fold resistance to taxol and exhibited cross-resistance to other drugs including actinomycin D, doxorubicin, vinblastine, and vincristine. Expression levels of five human ß-tubulin isotypes (ß_I-, ß_II-, ß_III-, ß_Iva and ß_Ivb-tubulin) were examined by real-time semi-quantitative PCR. Comparing with QGY-7703 cells, QGY-TR50 cells did not show any significant change in the expression levels of ß_I-, ß_Iva and ß_Ivb-tubulin, while a 1.2-fold increase in ß_II-tubulin and a decrease in ß_III-tubulin levels were observed. The mdr1 gene encoded-protein, P-gp was highly expressed in QGY-TR50 cells, but did not have any detectable expression in QGY-7703 cells. It was proved that the mdr1 gene isolated from the QGY-TR50 cells was functional, and its protein product could rescue the QGY-7703 cells in the presence of high concentrations of taxol. On the other hand, applying a P-gp inhibitor, verapamil could completely block the drug-resistant ability of QGY-TR50 cells. All results suggest that the P-glycoprotein could be one key factor involved in enhancing drug-resistance in QGY-TR50 cells.

Date of Award	2001
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology