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

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.

• Authors: Xu Zhang, Yang Teng, Fang Yang, Meng Wang, Xuan Hong, Lei-Guang Ye, Yi-Na Gao, Gong-Yan Chen
• Journal: Oncology reports (Oncol Rep) Vol. 33 Issue 5 Pg. 2599-605 (May 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25738322 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCND1 protein, human
• Cell Cycle Proteins
• Cyclin-Dependent Kinase Inhibitor p21
• Retinoblastoma Protein
• TP53 protein, human
• Tumor Suppressor Protein p53
• Cyclin D1
• Lovastatin
• CDK4 protein, human
• Cyclin-Dependent Kinase 4
• MCM2 protein, human
• Minichromosome Maintenance Complex Component 2

Topics

• Apoptosis (drug effects, genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Cell Cycle Checkpoints (drug effects, genetics)
• Cell Cycle Proteins (genetics)
• Cell Line, Tumor
• Cyclin D1 (genetics)
• Cyclin-Dependent Kinase 4 (genetics)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• G1 Phase Cell Cycle Checkpoints (drug effects, genetics)
• Humans
• Lovastatin (pharmacology)
• Lung Neoplasms (drug therapy, genetics)
• MAP Kinase Signaling System (drug effects, genetics)
• Minichromosome Maintenance Complex Component 2 (genetics)
• Retinoblastoma Protein (genetics)
• Tumor Suppressor Protein p53 (genetics)