PMID- 35293663 OWN - NLM STAT- MEDLINE DCOM- 20220725 LR - 20220725 IS - 1095-8355 (Electronic) IS - 1065-6995 (Linking) VI - 46 IP - 8 DP - 2022 Aug TI - OSI-027 inhibits the tumorigenesis of colon cancer through mediation of c-Myc/FOXO3a/PUMA axis. PG - 1204-1214 LID - 10.1002/cbin.11792 [doi] AB - 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. CI - (c) 2022 International Federation for Cell Biology. FAU - Lou, Jie AU - Lou J AD - Department of Gastroenterology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. AD - Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China. FAU - Lv, Jian-Xin AU - Lv JX AD - Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China. FAU - Zhang, You-Ping AU - Zhang YP AD - Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China. FAU - Liu, Zhan-Ju AU - Liu ZJ AUID- ORCID: 0000-0003-2326-2268 AD - Department of Gastroenterology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. LA - eng GR - 2019A610336/Ningbo Natural Science Foundation, China/ PT - Journal Article DEP - 20220608 PL - England TA - Cell Biol Int JT - Cell biology international JID - 9307129 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Forkhead Box Protein O3) RN - 0 (Forkhead Transcription Factors) RN - 0 (Imidazoles) RN - 0 (OSI 027) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Triazines) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Apoptosis MH - *Apoptosis Regulatory Proteins/metabolism MH - Carcinogenesis MH - Cell Line, Tumor MH - Cell Transformation, Neoplastic MH - *Colonic Neoplasms/metabolism MH - Forkhead Box Protein O3/metabolism MH - Forkhead Transcription Factors/metabolism MH - Humans MH - Imidazoles MH - Proto-Oncogene Proteins/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - TOR Serine-Threonine Kinases MH - Triazines OTO - NOTNLM OT - OSI-027 OT - PUMA OT - c-Myc/FOXO3a OT - colon cancer EDAT- 2022/03/17 06:00 MHDA- 2022/07/26 06:00 CRDT- 2022/03/16 08:45 PHST- 2022/01/16 00:00 [revised] PHST- 2021/10/22 00:00 [received] PHST- 2022/03/13 00:00 [accepted] PHST- 2022/03/17 06:00 [pubmed] PHST- 2022/07/26 06:00 [medline] PHST- 2022/03/16 08:45 [entrez] AID - 10.1002/cbin.11792 [doi] PST - ppublish SO - Cell Biol Int. 2022 Aug;46(8):1204-1214. doi: 10.1002/cbin.11792. Epub 2022 Jun 8.