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Tamoxifen reverses the multi-drug-resistance of an established human cholangiocarcinoma cell line in combined chemotherapeutics

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Abstract

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 G2/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.

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Acknowledgments

All authors have no conflict of interests. The authors thank Shanghai Jiao Tong University Affiliated Sixth People’s Hospital for technical assistance during this study. This work was financially supported by National Natural Science Foundation of China (No. 30672044), the National Basic Research Program of China (No. 2008CB517403), and the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. BXJ0929).

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Authors and Affiliations

  1. Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, China

    Zhi-Hua Liu, Yan-Lei Ma, Peng Zhang, Yu-Kun Zhou & Huanlong Qin

  2. Department of Surgery, Shanxi Medical University, Taiyuan, Shanxi, 030001, China

    Yan-Ping He

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  1. Zhi-Hua Liu
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  2. Yan-Lei Ma
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Correspondence to Huanlong Qin.

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Liu, ZH., Ma, YL., He, YP. et al. Tamoxifen reverses the multi-drug-resistance of an established human cholangiocarcinoma cell line in combined chemotherapeutics. Mol Biol Rep 38, 1769–1775 (2011). https://doi.org/10.1007/s11033-010-0291-z

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