Department of Pathology, Nagoya University Graduate School of Medicine Nagoya, Japan; Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Med. 2012 Oct;1(2):218-29. doi: 10.1002/cam4.32. Epub 2012 Sep 13.
Resistance to platinum- and taxane-based chemotherapy is a major cause of treatment failure in ovarian cancer. Thus, it is necessary to develop a predictive marker and molecular target for overcoming drug resistance in ovarian cancer treatment. In a previous report, using an in vitro model, we found that the RET finger protein (RFP) (also known as tripartite motif-containing protein 27, TRIM27) confers cancer cell resistance to anticancer drugs. However, the significance of RFP expression in cancer patients remains elusive. In this study, we showed that RFP was expressed in 62% of ovarian cancer patients and its positivity significantly correlated with drug resistance. Consistent with clinical data, depletion of RFP by RNA interference (RNAi) in ovarian cancer cell lines, SKOV3 and HEY, significantly increased carboplatin- or paclitaxel-induced apoptosis and resulted in reduced anticancer drug resistance. In a nude mouse tumor xenograft model, inoculated RFP-knockdown ovarian cancer cells exhibited lower carboplatin resistance than control cells. These findings suggest that RFP could be a predictive marker for chemoresistance in ovarian cancer patients and also a candidate for a molecular-targeted agent.
对铂类和紫杉烷类化疗药物的耐药性是卵巢癌治疗失败的主要原因。因此,有必要开发一种预测标志物和分子靶点,以克服卵巢癌治疗中的耐药性。在之前的一项研究中,我们使用体外模型发现,RET 手指蛋白(RFP)(也称为三结构域蛋白 27,TRIM27)使癌细胞对抗癌药物产生耐药性。然而,RFP 表达在癌症患者中的意义仍不清楚。在本研究中,我们表明 RFP 在 62%的卵巢癌患者中表达,其阳性表达与耐药性显著相关。与临床数据一致的是,在卵巢癌细胞系 SKOV3 和 HEY 中,通过 RNA 干扰(RNAi)耗尽 RFP 显著增加了顺铂或紫杉醇诱导的细胞凋亡,并降低了抗癌药物的耐药性。在裸鼠肿瘤异种移植模型中,接种 RFP 敲低的卵巢癌细胞比对照细胞表现出更低的顺铂耐药性。这些发现表明 RFP 可以作为卵巢癌患者化疗耐药性的预测标志物,也是一种潜在的分子靶向治疗药物。