Live-attenuated measles virus vaccine confers cell contact loss and apoptosis of ovarian cancer cells via ROS-induced silencing of E-cadherin by methylation.
Live-attenuated measles virus vaccine confers cell contact loss and apoptosis of ovarian cancer cells via ROS-induced silencing of E-cadherin by methylation.
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DOI：
10.1016/j.canlet.2011.10.038
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发表时间：
2012-05
期刊：
影响因子：
9.7
通讯作者：
Shengtao Zhou;Yuhua Li;Fuqiang Huang;Boya Zhang;T. Yi;Zhengyu Li;Hong Luo;Xiang He;Qian Zhong;C. Bian;Xiaojuan Lin;Xiaorong Qi;Ping Liu;Canhua Huang;Xia Zhao;Yuquan Wei
中科院分区：
文献类型：
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作者：
Shengtao Zhou;Yuhua Li;Fuqiang Huang;Boya Zhang;T. Yi;Zhengyu Li;Hong Luo;Xiang He;Qian Zhong;C. Bian;Xiaojuan Lin;Xiaorong Qi;Ping Liu;Canhua Huang;Xia Zhao;Yuquan Wei
在此，我们提出了麻疹病毒（MV）减毒活疫苗对卵巢癌抗肿瘤作用的新分子机制。使用基于2-DE/MS的比较蛋白质组学策略，我们鉴定了减毒活MV疫苗处理的SKOV-3卵巢癌细胞中差异表达的17种蛋白质，包括氧化应激相关酶和细胞接触相关蛋白，这表明减毒活MV疫苗可以诱导异常ROS激活。它通过上调 DNMT3a 进一步介导 E-钙粘蛋白的表观遗传沉默，从而导致细胞与细胞和细胞与基质接触丧失和卵巢癌细胞凋亡。这一过程可以通过 ROS 抑制来逆转。我们的研究为MV减毒活疫苗作为卵巢癌潜在治疗剂的临床应用奠定了理论基础。
Herein we present a novel molecular mechanism of the antitumor effects of live-attenuated measles virus (MV) vaccine in ovarian cancer. Using a 2-DE/MS-based comparative proteomics strategy, we identified 17 proteins differentially expressed in live-attenuated MV vaccine-treated SKOV-3 ovarian cancer cells, including oxidative stress-associated enzymes and cell contact-related proteins, which indicated that live-attenuated MV vaccine could induce aberrant ROS activation. It further mediated epigenetic silencing of E-cadherin via upregulating DNMT3a that conferred both cell–cell and cell–matrix contact loss and apoptosis of ovarian cancer cells. This process could be reversed through ROS inhibition. Our study lays the theoretical foundation for the clinical application of live-attenuated MV vaccine as a potential oncotherapeutic agent for ovarian cancer treatment.