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信号转导与转录激活因子3(STAT3)诱饵寡脱氧核苷酸对人上皮性卵巢癌细胞侵袭和化疗敏感性的作用

Role of STAT3 decoy oligodeoxynucleotides on cell invasion and chemosensitivity in human epithelial ovarian cancer cells.

作者信息

Zhang Xiaolei, Liu Peishu, Zhang Bo, Wang Ancong, Yang Meixiang

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wen-hua Xi Road, Jinan, Shandong Province, P.R. China.

出版信息

Cancer Genet Cytogenet. 2010 Feb;197(1):46-53. doi: 10.1016/j.cancergencyto.2009.10.004.

Abstract

Recent studies have reported that STAT3 activation is associated with poor prognosis in human epithelial ovarian cancer. STAT3 has been proposed to play an important role in ovarian cancer metastasis and chemoresistance. This mechanism, however, is still not thoroughly understood. In this study, to investigate the role of STAT3 on ovarian cancer cells, we used decoy oligodeoxynucleotide (ODN) technology to regulate STAT3 in SKOV3 and OVCAR3 cells in vitro. Cell invasive power and chemo-sensitivity were assessed in the cells transfected with STAT3 decoy ODN and control ODN. Western blot analysis was used to examine the expression of EMMPRIN, P-gp, and Akt. Results showed that STAT3 decoy ODN inhibited cancer cell invasive power and enhanced sensitivity to paclitaxel for SKOV3 and OVCAR3 cells. The mechanism involved the inhibition of EMMPRIN, P-gp, and pAkt by STAT3 decoy ODN. These three proteins were probably the target proteins of STAT3. These findings suggest that STAT3 is a key factor for ovarian cancer metastasis and chemoresistance. STAT3 decoy ODN may prove to be a beneficial therapeutic agent, especially for invasive or chemoresistant ovarian cancer.

摘要

近期研究报道,信号转导与转录激活因子3(STAT3)的激活与人上皮性卵巢癌的不良预后相关。STAT3被认为在卵巢癌转移和化疗耐药中起重要作用。然而,这一机制仍未被完全理解。在本研究中,为了探究STAT3在卵巢癌细胞中的作用,我们使用诱饵寡脱氧核苷酸(ODN)技术在体外对SKOV3和OVCAR3细胞中的STAT3进行调控。对转染了STAT3诱饵ODN和对照ODN的细胞进行细胞侵袭能力和化疗敏感性评估。采用蛋白质免疫印迹分析检测细胞外基质金属蛋白酶诱导因子(EMMPRIN)、P-糖蛋白(P-gp)和蛋白激酶B(Akt)的表达。结果显示,STAT3诱饵ODN抑制了SKOV3和OVCAR3细胞的癌细胞侵袭能力,并增强了其对紫杉醇的敏感性。其机制包括STAT3诱饵ODN对EMMPRIN、P-gp和磷酸化Akt的抑制作用。这三种蛋白可能是STAT3的靶蛋白。这些发现表明,STAT3是卵巢癌转移和化疗耐药的关键因素。STAT3诱饵ODN可能是一种有益的治疗药物,尤其是对于侵袭性或化疗耐药的卵巢癌。

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