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, Sze Chuen Cesar Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

17 Citations (Scopus)

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 IC50of 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
Pages (from-to)292-296
Number of pages5
JournalOncology
Volume71
Issue number3-4
DOIs
Publication statusPublished - 1 Aug 2007
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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