molecular mechanism of chemoresistance in ovarian cancer cells

本研究旨在探讨卵巢癌细胞耐药的分子机制，寻找克服卵巢癌细胞耐药的分子靶点。我们报道了一种抗凋亡分子clusterin在紫杉醇耐药的卵巢癌细胞中表达上调，针对clusterin的si-RNA或反义寡核苷酸的引入使紫杉醇敏感，卵巢癌组织中clusterin的免疫反应性与化疗反应呈负相关，是早期卵巢癌的预测因子。我们还报道了microRNA-31（miR-31）在卵巢癌紫杉醇耐药细胞中的表达较亲本细胞下调，将miR-31增敏的卵巢癌紫杉醇耐药细胞导入紫杉醇，受体酪氨酸激酶MET是直接靶分子，MET可能参与了卵巢癌紫杉醇耐药的机制，MET抑制剂可使卵巢癌紫杉醇耐药细胞对紫杉醇增敏。

We aimed to investigate the molecular mechanism of chemoresistance and to find molecular targets to overcome chemoresistance in ovarian cancer cells. We reported that clusterin, an antiapoptotic molecule, is upregulated in paclitaxel-resistant ovarian cancer cells compared to parental cells, introduction of si-RNA or antisenseoligonucleotide against clusterin sensitized paclitaxel-resistant ovarian cancer cells to paclitaxel,clusterin immunoreactivity in ovarian cancer tissues inversely correlates with response to chemotherapy and is a prognosticator for early-stage ovarian cancer. We also reported that microRNA-31 (miR-31) is down-regulated in paclitaxel-resistant ovarian cancer cells compared to parental cells, introduction of miR-31 senstized paclitaxel-rsistant ovarian cancer cells to paclitaxel, MET, a receptor tyrosine kinase, is a direct target molecule and MET can be involved in the resistant mechanisim against paclitaxel and MET inhibitor can sensitize paclitaxel-resistant ovarian cancer cells to paclitaxel.