Department of Gastroenterology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.
Cell Biol Int. 2022 Aug;46(8):1204-1214. doi: 10.1002/cbin.11792. Epub 2022 Jun 8.
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.
结直肠癌是一种胃肠道恶性肿瘤，是肿瘤相关死亡的主要原因之一。据报道，雷帕霉素靶蛋白（mTOR）可导致结直肠癌的进展。然而，mTOR 抑制剂（OSI-027）介导结直肠癌发生的机制在很大程度上尚不清楚。通过细胞计数试剂盒-8 流式细胞术和末端脱氧核苷酸转移酶 dUTP 缺口末端标记染色研究结直肠癌细胞的功能。此外，还使用定量实时聚合酶链反应和 Western blot 来研究 OSI-027 在结直肠癌中作用的机制。OSI-027 通过诱导细胞凋亡，呈剂量依赖性降低结直肠癌细胞活力。此外，OSI-027 通过上调 PUMA 诱导结直肠癌细胞凋亡。OSI-027 通过激活叉头框蛋白 O3a（FOXO3a）促进 PUMA 的表达，c-Myc 敲低部分增加 FOXO3a 和 PUMA 水平。此外，OSI-027 通过 mTOR/c-Myc/FOXO3a 轴介导抑制结直肠癌细胞的肿瘤生长。OSI-027 通过 c-Myc/FOXO3a/PUMA 轴抑制结直肠癌的进展。因此，本研究可能为探索对抗结直肠癌的策略提供新的思路。
