Tamoxifen reverses the multi-drug-resistance of an established human cholangiocarcinoma cell line in combined chemotherapeutics.
Our previous study established the human multi-drug-resistant cholangiocarcinoma cell line QBC939/ADM. In this study, we investigate further the ability of tamoxifen (TAM) to reverse drug-resistance to chemotherapeutics using QBC939/ADM cells. Cell growth inhibition was determined by the MTT assay, while cell cycle progression, apoptosis and the intra-cellular concentration of adriamycin (ADM) were all determined by flow cytometry. P-glycoprotein (P-gp) protein and mRNA expression was determined by Western blotting and real-time PCR. Growth inhibition and apoptosis induced by ADM, mitomycin (MMC), or vindesine (VDS) were enhanced after pre-treatment with 5 or 10 μM TAM, while only VDS increased cell numbers in the G(2)/M phase. The intra-cellular concentration of ADM rose after pre-treatment with 10 μM TAM, but not 5 μM TAM. Furthermore, real-time PCR and western blot analysis revealed down-regulation of P-gp expression in QBC939/ADM cells after TAM pre-treatment. The enhanced effects of TAM on growth inhibition, apoptosis, and intra-cellular concentration and the down-regulation of P-gp expression were blocked by an anti-P-gp antibody. TAM (10 μM) may reverse the multi-drug-resistance (MDR) of QBC939/ADM and enhance the chemotherapeutic effects on cholangiocarcinoma, by competitively inhibiting over-expressed P-gp.
Liu
Zhi-Hua
ZH
Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Ma
Yan-Lei
YL
He
Yan-Ping
YP
Zhang
Peng
P
Zhou
Yu-Kun
YK
Qin
Huanlong
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000235:genetics / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D016685:Mitomycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014751:Vindesine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D013629:Tamoxifen; D016685:Mitomycin; D004317:Doxorubicin; D014751:Vindesine