Effects of Patupilone (Epothilone B; EPO906), a Novel Chemotherapeutic Agent, in Hepatocellular Carcinoma: An in vitro Study

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 (IC(50)) 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.