OSI-027 inhibits the tumorigenesis of colon cancer through mediation of c-Myc/FOXO3a/PUMA axis

被引：10
作者：
Lou, Jie [1 ,2 ]
Lv, Jian-Xin [2 ]
Zhang, You-Ping [2 ]
Liu, Zhan-Ju [1 ]
机构：
[1] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Gastroenterol, Shanghai, Peoples R China
[2] Univ Chinese Acad Sci, HwaMei Hosp, Dept Gastroenterol, Ningbo, Zhejiang, Peoples R China
来源：
CELL BIOLOGY INTERNATIONAL | 2022年 / 46卷 / 08期
关键词：
c-Myc; FOXO3a; colon cancer; OSI-027; PUMA; PUMA-DEPENDENT APOPTOSIS; PROLIFERATION; RESISTANCE; PI3K/AKT; GROWTH;
D O I：
10.1002/cbin.11792
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Colon cancer is a gastrointestinal malignancy that is one of the leading causes of tumor-associated deaths. It has been reported that the mammalian target of rapamycin (mTOR) can lead to the progression of colon cancer. However, the mechanism by which mTOR inhibitor (OSI-027) mediates the tumorigenesis of colon cancer remains largely unknown. Cell function of colon cancer was investigated by cell counting kit-8 flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In addition, quantitative real-time polymerase chain reaction and Western blot were used to investigate the mechanism underlying the function of OSI-027 in colon cancer. OSI-027 dose-dependently reduced colon cancer cell viability by inducing cell apoptosis. In addition, OSI-027 induced the apoptosis of colon cancer cells via upregulation of PUMA. OSI-027 promoted the expression of PUMA by activation of forkhead box protein O3a (FOXO3a), and c-Myc knockdown partially increased FOXO3a and PUMA levels. Moreover, OSI-027 attenuated the tumor growth of colon cancer through the mediation of the mTOR/c-Myc/FOXO3a axis. OSI-027 attenuates colon cancer progression through the mediation of the c-Myc/FOXO3a/PUMA axis. Thereby, this study might shed new insights on exploring the strategies against colon cancer.
引用
收藏
页码：1204 / 1214
页数：11
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