NOX4调控非小细胞肺癌EMT转化及侵袭转移的研究

项目名称： NOX4调控非小细胞肺癌EMT转化及侵袭转移的研究

项目编号： No.81201622

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 刘冰

作者单位： 广东药学院

项目金额： 23万元

中文摘要： 近来研究提示NOX与肿瘤的恶性进展密切相关，然而至今尚无揭示NOX调控肿瘤细胞EMT转化及侵袭转移的直接证据。我们前期研究发现：在低侵袭性非小细胞肺癌（NSCLC）细胞H292中过表达NOX4可促进细胞侵袭，并可抑制E-cadherin表达；此外，NOX4过表达可上调细胞内ROS水平，并可激活PI3K-Akt和Erk MAPK信号通路。用NOX功能抑制剂DPI抑制ROS产生后，NOX4介导的上述效应被阻断。目前已知：PI3K-Akt和Erk MAPK信号通路的持续激活在调控多种肿瘤细胞EMT转化中起关键作用。据此，我们提出"NOX4通过介导ROS生成激活PI3K-Akt和Erk MAPK信号通路从而促进NSCLC细胞发生EMT转化及侵袭转移"这一研究假设。为证实该假设，本研究在上述基础上，通过不同水平深入探讨NOX4对NSCLC细胞EMT转化及侵袭转移的影响及其机制，以期获得新的干预靶点。

中文关键词： 非小细胞肺癌；NADPH氧化酶；上皮间质转化；增殖；白细胞介素6

英文摘要： Recently, several studies suggest a close correlation between NADPH oxidase (NOX) and cancer malignant progression. However, there have been no direct evidences confirming that NOX can regulate tumor cell epithelial-mesenehymal transition (EMT) and subsequent invasion and metastasis. Our preliminary study showed that overexpression of NOX4 in low aggressive H292 cells (a non-small cell lung cancer (NSCLC) cell line) enhanced the invasive ability and reduced E-cadherin expression. Forced NOX4 expression increased the level of intracellular reactive oxygen species (ROS) and led to activation of PI3K-Akt and Erk MAPK pathways. Furthermore, we found that DPI (a NADPH oxidase inhibitor) treatment could block the above effects induced by NOX4 overexpression. Sustained activation of PI3K-Akt and Erk MAPK pathways has been confirmed to play a critical role in regulation of EMT of various cancer cells. Thus, we propose that NOX4-mediated ROS production can promote EMT, invasion and metastasis of NSCLC cells, possibly through activation of PI3K-Akt and Erk MAPK pathways. To demonstrate the hypothesis, based on our previous findings, this study will further explore the effect of NOX4 on EMT, invasion and metastasis of NSCLC cells as well as the molecular mechanisms at various experimental levels to find a new molecular ta

英文关键词： Non-small cell lung carcinoma；NADPH oxidase；Epithelial-Mesenchymal Transition；Proliferation；IL-6