molecular mechanism of chemoresistance in ovarian cancer cells

我们的目标是研究卵巢癌细胞化疗耐药的分子机制，寻找克服卵巢癌细胞化疗耐药的分子靶点。我们报道了在紫杉醇耐药的卵巢癌细胞中，与亲本细胞相比，抗凋亡分子Clusterin的表达上调，将针对Clusterin敏感的紫杉醇耐药卵巢癌细胞的si-RNA或反义寡核苷酸引入紫杉醇，卵巢癌组织中的Clusterin免疫反应与化疗反应呈负相关，是早期卵巢癌的预后指标。我们还报道了microRNA-31(miR-31)在紫杉醇耐药卵巢癌细胞中的表达下调，将miR-31敏感的紫杉醇耐药卵巢癌细胞导入紫杉醇，MET，一种受体酪氨酸激酶，是紫杉醇耐药的直接靶分子，MET可以参与紫杉醇的耐药机制，MET抑制剂可以使紫杉醇耐药的卵巢癌细胞对紫杉醇增敏。

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.