Class I phosphatidylinositol 3-kinase inhibitor LY294002 activates autophagy and induces apoptosis through p53 pathway in gastric cancer cell line SGC7901

被引:46
|
作者
Xing, Chungen [1 ]
Zhu, Baosong [1 ]
Liu, Huihui [2 ]
Yao, Huihua [1 ]
Zhang, Lifeng [3 ]
机构
[1] Soochow Univ, Affiliated Hosp 2, Dept Gen Surg, Suzhou 215004, Peoples R China
[2] Soochow Univ, Affiliated Hosp 2, Dept Neurol, Suzhou 215004, Peoples R China
[3] Soochow Univ, Sch Med, Suzhou 215123, Peoples R China
关键词
PI3K; LY294002; autophagy; apoptosis;
D O I
10.1111/j.1745-7270.2008.00393.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We aimed to study the effects of LY294002, an inhibitor of class I phosphatidylinositol 3-kinase (PI3K), on proliferation, apoptosis, and autophagy in gastric cancer cell line SGC7901. In this study, we showed that LY294002 inhibited the viability of gastric cancer SGC7901 cells. We also showed that LY294002 increased the expression of microtubule-associated protein 1 light chain 3 (LC3), and increased monodansylcadaverine (MDC)-labeled vesicles. LY294002 activated autophagy by activating p53 and caspase-3, and induced apoptosis by up-regulatingp53 and p53-up-regulated modulator of apoptosis (PUMA). Therefore, LY294002 might induce cytotoxicity in SGC7901 cells through activation of p53 and the downstream point PUMA. These findings suggest that inhibition of the class I PI3K signaling pathway is a potential strategy for managing gastric cancers.
引用
收藏
页码:194 / 201
页数:8
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