MCM2 is a therapeutic target of lovastatin in human non-small cell lung carcinomas

Zhang,Xu; Teng,Yang; Yang,Fang; Wang,Meng; Hong,Xuan; Ye,Lei-Guang; Gao,Yi-Na; Chen,Gong-Yan

doi:10.3892/or.2015.3822

MCM2 is a therapeutic target of lovastatin in human non-small cell lung carcinomas

Authors:
- Xu Zhang
- Yang Teng
- Fang Yang
- Meng Wang
- Xuan Hong
- Lei-Guang Ye
- Yi-Na Gao
- Gong-Yan Chen
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Affiliations: Department of Stomatology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China, Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China
Published online on: February 27, 2015 https://doi.org/10.3892/or.2015.3822
Pages: 2599-2605

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Abstract

Human non-small cell lung carcinoma (NSCLC) is one of the most common cancer worldwide. In previous studies, lovastatin, acting as an inhibitor of 3-hydroxy‑3-methylglutaryl Co A (HMG-CoA) reductase, exhibited significant antitumor activity during tumorigenesis. However, whether or not this effect is mediated through changes in minichromosome maintenance (MCM) 2 expression remains unclear. The present study investigated whether lovastatin inhibits proliferation due to MCM2 in NSCLCs. We first assessed the effects of lovastatin on cell anti-proliferation, cell cycle progression and apoptosis in NSCLC cells. We found, by quantitative RT-PCR and western blot analysis, that lovastatin treatment markedly and consistently inhibited the expression of MCM2. Then, to further explore the anticancer mechanism of lovastatin involving MCM2, we silenced MCM2 by siRNA in two cell lines (A549 and GLC-82). Silencing of MCM2 triggered G1/S arrest. Following further examination of cell cycle-related factors, MCM2 knockdown inhibited protein retinoblastoma (Rb), cyclin D1 and CDK4 expression, but increased p21 and p53 expression, suggesting that siMCM2 indeed triggered cell cycle arrest. In addition, siMCM2 induced apoptosis. Finally, lovastatin treatment increased p-JNK, which is involved in the downregulation of MCM2. In conclusion, our data suggest that MCM2 may be a novel therapeutic target of lovastatin treatment in NSCLCs.

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