Study of multi-drug resistant mechanisms in a taxol-resistant hepatocellular carcinoma QGY-TR 50 cell line

Cancer chemotherapy with taxol often fails due to acquired resistance of ca ncer cells, which is frequently associated with an overexpression of P-gp a nd alterations of beta -tubulin. A taxol-resistant cell line, QGY-TR50, der ived from a human hepatocellular carcinoma (HCC) QGY-7703 cell line was use d to investigate the mechanisms of taxol-resistance, QGY-TR50 cells showed more than 250-fold resistance to taxol and exhibited cross-resistance to ot her drugs including actinomycin D, doxorubicin, vinblastine, and vincristin e, P-gp was highly expressed in QGY-TR50 cells. Expression levels of five h uman beta -tubulin isotypes (beta (I), beta (II)-, beta (III)-, beta (IVa), and beta (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 beta (I)-, beta (IVa), and beta (IVb)-tu bulin, While a 1.2-fold increased in beta (II)-tubulin and a 0.5-fold decre ased in beta (III)-tubulin levels were observed. All results suggest that t he P-glycoprotein could be one key factor involved in enhancing drug resist ance in QGY-TR50 cells. (C) 2001 Academic Press.