蛋白磷酸酶2A在NO供体诱导肝癌细胞凋亡中的调节作用

项目名称： 蛋白磷酸酶2A在NO供体诱导肝癌细胞凋亡中的调节作用

项目编号： No.81502627

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘玲

作者单位： 河南科技大学

项目金额： 18万元

中文摘要： 一氧化氮（Nitric Oxide, NO）在肿瘤的发生、发展中具有重要的调节作用；而蛋白磷酸酶2A（protein phosphatase 2A, PP2A）作为肿瘤抑制因子，通过调控多种信号通路可引起细胞凋亡。而MAPK、PI3K-Akt和Wnt/β-catenin等信号通路是两者的交汇点。前期研究发现，NO供体能提高HepG2肝癌细胞内NO水平，激活MAPK等信号通路而诱导细胞凋亡；PP2A抑制剂冈田酸可减弱NO供体对肝癌细胞的凋亡诱导作用。本项目旨从PP2A角度探讨NO供体诱导肝癌细胞凋亡的分子机制，采用偶氮鎓二醇盐衍生物JS-K作为NO供体，结合RNAi技术和特异性抑制剂/激动剂，建立可调控PP2A表达的肝癌细胞系和动物模型，围绕PP2A检测与其在凋亡调控中密切相关的MAPK、PI3K-Akt和Wnt/β-catenin等信号通路的变化，为研究NO供体的抗肿瘤作用提供新的切入点。

中文关键词： 一氧化氮；蛋白磷酸酶2A；细胞凋亡；肝细胞癌

英文摘要： Nitric oxide (NO) is a signaling molecule with a broad spectrum of actions in carcinogenesis, cell cycle regulation, and apoptosis processes. Protein phosphatase 2A (PP2A) is widely described as a tumor suppressor and takes part in the majority of the cellular pathways to induce apoptosis. The MAPK, PI3K-Akt and Wnt/β-catenin signaling pathway is a meeting point between the NO donor and PP2A.Our previous study indicated that NO released from NO donor could induce human hematoma HepG2 cells apoptosis through a MAPK-mediated mitochondrial pathway. Treatment with okadaic acid (an inhibitor of PP2A) prior to NO donor was found to partly reverse NO donor-induced apoptosis. To investigate the molecular mechanisms of NO donor-induced apoptosis of hepatoma cells from PP2A aspects, this study will establish the human hematoma cells and hepatocellular carcinoma in rats combined with RNAi technology and specific inhibitor/agonists that can regulate the expression of PP2A. Diazeniumdiolate -based derivatives JS-K as NO donor will be used to detect the changes of PP2A in the regulation of apoptosis which is closely related MAPK, PI3K-Akt and Wnt/β-catenin signaling pathway, etc, which will provide a new entry point for the anti-tumor effect of NO donor.

英文关键词： Nitric oxide;Protein phosphatase 2A ;Cell apoptisis ;Hepatocellular