Effects of patupilone (epothilone B; EPO906), a novel chemotherapeutic agent, in hepatocellular carcinoma: An in vitro study

Tony S.K. Mok, Eve Choi, Daisy Yau, Anandhi Johri, Winnie Yeo, Anthony T.C. Chan, Cesar Wong

    Research output: Contribution to journalArticle

    17 Scopus citations

    Abstract

    Purpose: In this study, the cytotoxic effects of patupilone (epothilone B; EPO906) were assessed in a panel of hepatocellular carcinoma (HCC) cell lines, and were compared with doxorubicin and the microtubule-stabilizing taxanes. Methods: The following HCC cell lines were used: PLC/PRF/5, HepG2, Hep3B, SNU-387, SNU-398, SNU-423, SNU-449, and SNU-475. Cells were treated with various concentrations of patupilone, paclitaxel, docetaxel, or doxorubicin for 72 h; 50% inhibitory concentrations (IC50) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. P-glycoprotein expression was assessed using standard Western blotting techniques. Results: Patupilone was found to be the most potent drug in all 8 HCC cell lines. All cell lines except SNU-449 were 4- to19-fold more sensitive to patupilone than to paclitaxel and docetaxel, and 59- to 208-fold more sensitive than to doxorubicin. SNU-449, the most resistant cell line and the only one overexpressing P-glycoprotein, was 3- to 39-fold more resistant to paclitaxel, docetaxel, and doxorubicin than were other cell lines. The IC 50 of patupilone in SNU-449 was 1.14 nmol, which was 108- to 529-fold lower than those of the other agents. Conclusion: Patupilone was more potent than taxanes and doxorubicin in HCC cell lines and may result in reduced clinical resistance by overcoming P-glycoprotein overexpression. A clinical study in HCC is warranted.

    Original languageEnglish (US)
    Pages (from-to)292-296
    Number of pages5
    JournalOncology
    Volume71
    Issue number3-4
    DOIs
    StatePublished - Aug 1 2007

    Keywords

    • Doxorubicin
    • Epothilone B
    • Hepatocellular carcinoma
    • P-glycoprotein
    • Patupilone
    • Taxane

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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    Mok, T. S. K., Choi, E., Yau, D., Johri, A., Yeo, W., Chan, A. T. C., & Wong, C. (2007). Effects of patupilone (epothilone B; EPO906), a novel chemotherapeutic agent, in hepatocellular carcinoma: An in vitro study. Oncology, 71(3-4), 292-296. https://doi.org/10.1159/000106450