维普中文期刊产品整合服务

DJ-1 is involved in the multidrug resistance of SGC7901 gastric cancer cells through PTEN/PI3K/Akt/Nrf2 pathway

查看全文 作　　者：Lejia [1]Qiu;Zhaoxia [1]Ma;Xiaoran [1]Li;Yizhang [1]Deng;Guangling [1]Duan;Le [1]Zhao;Xingwang [1]Xu;Lin [1]Xiao;Haoyue [1]Liu;Zhengming [1]Zhu;Heping [1]Chen 高影响力作者 机构地区：[1]The Key Laboratory of Basic Pharmacology,Schoo of Pharmaceutical Science,Nanchang University,Nanchang 330006,China,and 2Department of General Surgery,The Second Affiliated Hospital of Nanchang University,Nanchang 330006,China高影响力机构 出　　处：《Acta Biochimica et Biophysica Sinica》索引2020年第52卷第11期,共13页高影响力期刊 基　　金：the grants from the National Natural Science Foundation of China(No.81560389);Nanchang University Innovation Special Fund Project of Graduates(No.CX2017233). 摘　　要：Gastric cancer is a common malignancy worldwide.The occurrence of multidrug resistance(MDR)is the major obstacle for effective gastric cancer chemotherapy.In this study,the in-depth molec-ular mechanism of the DJ-1-induced MDR in SGC7901 gastric cancer cells was investigated.The results showed that DJ-1 expression level was higher in MDR variant SGC7901NCR cells than that in its parental SGC7901 cells.Moreover,DJ-1 overexpression conferred the MDR phenotype to SGC7901 cells,while DJ-1 knockdown in SGC7901NCR cells induced re-sensitization to adriamycin,vincristine,cisplatin,and 5-fluorouracil.These results suggested that DJ-1 mediated the develop-ment of MDR in SGC7901 gastric cancer cells.Importantly,further data revealed that the activation of PI3k/Akt and Nrf2 signaling pathway were required for the DJ-1-induced MDR phenotype in SGC7901 gastric cancer cells.Meanwhile,we found that Pl3k/Akt pathway was activated probably through DJ-1 directly binding to and negatively regulating PTEN,consequently resulting in Nrf2 phosphorylation and activation,and thereby inducing Nrf2-dependent P-glycoprotein(P-gp)and Bcl-2 expressions in the DJ-1-mediated MDR of SGC7901 gastric cancer cells.Overall,these results revealed that activating PTEN/PI3K/Akt/Nrf2 pathway and subsequently upregulating P-gp and Bcl-2 expression could be a critical mechanism by which DJ-1 mediates the development of MDR in SGC7901 gastric cancer cells.The new findings may be helpful for understanding the mechanisms of MDR in gastric cancer cells,prompting its further investigation as a molecular target to overcome MDR. 关 键 词：gastric cancer multidrug resistance DJ-1 PTEN/PI3K/Akt signaling pathway Nrf2 signaling pathway
相关文献

参考文献(36)

引证文献(8)

网站首页 | 关于我们 | 联系我们 | 产品服务 | 客服中心 | 广告服务 | 版权声明 | 网站联盟 | 友情链接 | 售卡网点

版权所有© 渝B2-20050021-1　渝公网安备 50019002500403号　违法和不良信息举报中心

互联网出版许可证 新出网证(渝)字10号 全国400电话 - 免长途话费