Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway
Authors Jiang W, Chen Y, Song X, Shao Y, Ning Z, Gu W
Received 28 January 2019
Accepted for publication 8 April 2019
Published 23 April 2019 Volume 2019:12 Pages 3043—3050
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Sanjeev Srivastava
Wenjie Jiang,1 Yuan Chen,1 Xing Song,1 Yingjie Shao,1 Zhonghua Ning,1 Wendong Gu1
1Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou 213003, People’s Republic of China
Background: In the present study, we aimed to investigate the effect of proviral integration site for moloney murine leukemia virus-1 (Pim-1) inhibitor (SMI-4a) on the progression of non-small cell lung cancer (NSCLC).
Materials and methods: The effects of SMI-4a on proliferation, apoptosis, and cell cycle of NSCLC cells were examined by in vitro experiments using human NSCLC cell lines (A549 and Ltep-a-2). The pathway regulated by SMI-4a was detected using Western blot. Furthermore, we performed in vivo experiments to assess the effects of SMI-4a on tumor growth using mouse models with NSCLC.
Results: Our data demonstrated that SMI-4a could inhibit the proliferation of A549 and Ltep-a-2 cells markedly in a dose-dependent manner (P<0.05). Treatment with 80 μmol/L of SMI-4a for 48 h significantly induced the apoptosis rate of NSCLC cells (P<0.05), and blocked the cell cycle of NSCLC cells in G2/M phase (P<0.05). The phosphorylation levels of PI3K, AKT, and mTOR in NSCLC cells were significantly downregulated by SMI-4a (P<0.05). Result from in vivo experiments demonstrated that SMI-4a could suppress the tumor growth in mouse models with NSCLC (P<0.05).
Conclusions: SMI-4a suppresses the progression of NSCLC by blocking the PI3K/AKT/mTOR pathway.
Keywords: Pim-1, SMI-4a, NSCLC, tumor progression
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