Mok Tony S K, Choi Eve, Yau Daisy, Johri Anandhi, Yeo Winnie, Chan Anthony T C, Wong Cesar
Department of Clinical Oncology, State Key Laboratory in Oncology in South China and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Oncology. 2006;71(3-4):292-6. doi: 10.1159/000106450. Epub 2007 Jul 26.
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.
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.
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.
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.
在本研究中，评估了帕妥珠利（埃坡霉素B；EPO906）对一组肝癌（HCC）细胞系的细胞毒性作用，并与阿霉素和微管稳定紫杉烷类进行了比较。
使用了以下肝癌细胞系：PLC/PRF/5、HepG2、Hep3B、SNU-387、SNU-398、SNU-423、SNU-449和SNU-475。细胞用不同浓度的帕妥珠利、紫杉醇、多西他赛或阿霉素处理72小时；通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐法测定50%抑制浓度（IC(50)）。使用标准蛋白质印迹技术评估P-糖蛋白表达。
发现帕妥珠利在所有8种肝癌细胞系中是最有效的药物。除SNU-449外，所有细胞系对帕妥珠利的敏感性比对紫杉醇和多西他赛高4至19倍，比对阿霉素高59至208倍。SNU-449是最耐药的细胞系，也是唯一过表达P-糖蛋白的细胞系，对紫杉醇、多西他赛和阿霉素的耐药性比其他细胞系高3至39倍。帕妥珠利在SNU-449中的IC(50)为1.14 nmol，比其他药物低108至529倍。
在肝癌细胞系中，帕妥珠利比紫杉烷类和阿霉素更有效，并且可能通过克服P-糖蛋白过表达而降低临床耐药性。有必要在肝癌中进行临床研究。
