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 cancer cells, which is frequently associated with an overexpression of P-gp and alterations of beta-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. P-gp was highly expressed in QGY-TR50 cells. Expression levels of five human beta-tubulin isotypes (betaI-, betaII-,betaIII-, betaIva, and betaIvb-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 betaI-, betaIva, and betaIvb-tubulin. While a 1.2-fold increased in betaII-tubulin and a 0.5-fold decreased in betaIII-tubulin levels were observed. All results suggest that the P-glycoprotein could be one key factor involved in enhancing drug resistance in QGY-TR50 cells.
Zhou
J
J
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, China.
Cheng
S C
SC
Luo
D
D
Xie
Y
Y
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D016685:Mitomycin / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014404:Tubulin / Q000235:genetics; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D020033:Protein Isoforms; D012334:RNA, Neoplasm; D014404:Tubulin; D003609:Dactinomycin; D016685:Mitomycin; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D017239:Paclitaxel; D005472:Fluorouracil