TRAP1，一种新型线粒体伴侣蛋白，在人类结肠癌细胞中负责多药耐药及抗凋亡。
TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells.
作者信息
Costantino Eleonora, Maddalena Francesca, Calise Serena, Piscazzi Annamaria, Tirino Virginia, Fersini Alberto, Ambrosi Antonio, Neri Vincenzo, Esposito Franca, Landriscina Matteo
机构信息
Clinical Oncology Unit, Department of Medical Sciences, University of Foggia, Viale Pinto 1, 71100 Foggia, Italy.
出版信息
Cancer Lett. 2009 Jun 28;279(1):39-46. doi: 10.1016/j.canlet.2009.01.018. Epub 2009 Feb 12.
TRAP1 is a component of a pro-survival mitochondrial pathway up-regulated in tumor cells. The evaluation of TRAP1 expression in 26 human colorectal carcinomas showed up-regulation in 17/26 tumors. Accordingly, TRAP1 levels were increased in HT-29 colorectal carcinoma cells resistant to 5-fluorouracil, oxaliplatin and irinotecan. Thus, we investigated the role of TRAP1 in multi-drug resistance in human colorectal cancer. Interestingly, TRAP1 overexpression leads to 5-fluorouracil-, oxaliplatin- and irinotecan-resistant phenotypes in different neoplastic cells. Conversely, the inhibition of TRAP1 activity by TRAP1 ATPase antagonist, shepherdin, increased the sensitivity to oxaliplatin and irinotecan in colorectal carcinoma cells resistant to the single agents. These results suggest that the increased expression of TRAP1 could be part of a pro-survival pathway responsible for multi-drug resistance.
TRAP1是肿瘤细胞中上调的一种促生存线粒体途径的组成部分。对26例人类结直肠癌中TRAP1表达的评估显示，17/26例肿瘤中TRAP1表达上调。相应地，在对5-氟尿嘧啶、奥沙利铂和伊立替康耐药的HT-29结肠癌细胞中，TRAP1水平升高。因此，我们研究了TRAP1在人类结直肠癌多药耐药中的作用。有趣的是，TRAP1过表达导致不同肿瘤细胞出现对5-氟尿嘧啶、奥沙利铂和伊立替康的耐药表型。相反，TRAP1 ATP酶拮抗剂shepherdin对TRAP1活性的抑制增加了对单一药物耐药的结肠癌细胞对奥沙利铂和伊立替康的敏感性。这些结果表明，TRAP1表达增加可能是负责多药耐药的促生存途径的一部分。
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