Molecular characterisation of two human cancer cell lines selected in vitro for their chemotherapeutic drug resistance to ET-743

被引:20
作者
Marchini, S
Marrazzo, E
Bonomi, R
Chiorino, G
Zaffaroni, M
Weissbach, L
Hornicek, FJ
Broggini, M
Faircloth, GT
D'Incalci, A
机构
[1] Mario Negri Inst Pharmacol Res, Dept Oncol, Mol Pharmacol Lab, I-20157 Milan, Italy
[2] Fondo Edo Tempia, I-13900 Biella, Italy
[3] Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA
[4] Harvard Univ, Sch Med, Boston, MA 02114 USA
[5] PharmaMar USA, Cambridge, MA 02139 USA
关键词
microarrays; ET-743; drug-resistant cells;
D O I
10.1016/j.ejca.2004.10.021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
ET-743 (Yondelis(TM), Trabectedin) isolated from the tunicate Ecteinascidia turbinata, is being tested in phase II clinical trials in Europe and the United States of America (USA). Studies with different solid tumours have shown antitumour activity in advanced, pre-treated sarcomas as well as in drug-resistant breast and ovarian cancer. The primary mechanism of action for ET-743 has not been fully elucidated and different models have been suggested to explain its molecular mechanism of action. ET-743 binds tightly to the minor groove of DNA and previous data have suggested that ET-743 acts by interfering with RNA transcription. To further investigate the mechanism of in vitro drug resistance, we evaluated the gene expression profile in ovarian and chondrosarcoma cell lines selected for resistance to ET-743. We found 70 genes whose expression was modulated in both drug-resistant cell lines when compared with their respective parental drug-sensitive cell lines. This pattern of gene expression seems to be selective for ET-743-resistant cells, since ovarian cancer cells resistant to paclitaxel did not share the same gene expression changes. Data presented in this study reveal different molecular pathways that could be involved in the cellular mechanism of ET-743 resistance. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:323 / 333
页数:11
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