The growth-inhibition effect of tamoxifen in the combination chemotherapeutics on the human cholangiocarcinoma cell line QBC939.
In the individual application of adriamycin, mitomycin, vindesine and their combined application with tamoxifen for the pre-treatment of the human cholangiocarcinoma cell line QBC939, QBC939 was determined by MTT assay to investigate the inhibitive effect and its initial mechanism of TAM on cell growth. Growth cycle and apoptosis of each group were determined by flow cytometry. Concentration of ADM in QBC939 was detected by flow cytometry. The levels of their P-glycoprotein were detected by immunohistochemistry. The mRNA and protein levels of apoptotic-associated genes Bcl-2 and Bax were determined by western blot and real-time PCR. The inhibitive rates of adriamycin, mitomycin, vindesine to QBC939 and the apoptosis rates of QBC939 were enhanced after the pre-treatment of tamoxifen. Influence of tamoxifen in their growth cycle was not so obvious except vindesine group because of the increasing cell numbers of G (2)/M phase in which cells may be blocked. The contents of adriamycin in cells rose after the pre-treatment of tamoxifen. Expression level of the multi-drug resistant protein on cell surface was shown as (+). Furthermore, real-time PCR and Western blot analysis revealed an upregulation of Bcl-2 and a downregulation of Bax in QBC939 after the pre-treatment of tamoxifen. Therefore, tamoxifen may have the ability to enhance the relative sensitivity of QBC939 to chemotherapeutics.
Liu
Zhi-Hua
ZH
Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, 200233 Shanghai, China.
He
Yan-Ping
YP
Qin
Huanlong
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D051028:bcl-2-Associated X Protein; D013629:Tamoxifen; D004317:Doxorubicin