Preclinical Activity of Simvastatin Induces Cell Cycle Arrest in G1 via Blockade of Cyclin D-Cdk4 Expression in Non-Small Cell Lung Cancer (NSCLC)

International Journal of Molecular Sciences

Yu-Wei Liang⁵  Chi-Chang Chang³  Chao-Ming Hung⁴  Tzu-Yu Chen¹  Tzuu-Yuan Huang² 

[1] Innovative Research Center of Medicine, College of Health Sciences, Chang Jung Christian University, Tainan 71101, Taiwan; E-Mail:;Departments of Neurosurgery, Tainan Sin-Lau Hospital, Tainan 70142, Taiwan; E-Mail:;Department of Obstetrics & Gynecology, E-Da Hospital, E-Da Hospital/I-Shou University, Kaohsiung 82445, Taiwan; E-Mail:;Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan; E-Mail:;Department of Emergency Medicine, Chi-Shan Hospital, Department of Health, Executive Yuan, Kaohsiung 84274, Taiwan; E-Mail:

关键词: simvastatin;    non-small cell lung cancer;    cell cycle arrest;    CyclinD-Cdk4;   

DOI  :  10.3390/ijms14035806

来源: mdpi

【 摘 要 】

Lung cancer is the most common cause of cancer-related death. Nonetheless, a decrease in overall incidence and mortality has been observed in the last 30 years due to prevention strategies and improvements in the use of chemotherapeutic agents. In recent studies, Simvastatin (SIM) has demonstrated anti-tumor activity, as well as potent chemopreventive action. As an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), SIM has been shown to stimulate apoptotic cell death. In this study, an MTT assay revealed the cytotoxic activity of SIM against human large cell lung cancer (Non-small cell lung cancer; NSCLC) cells (NCI-H460); however, induced apoptosis was not observed in NCI-H460 cells. Protein expression levels of cell cycle regulating proteins Cdk4, Cyclin D1, p16 and p27 were markedly altered by SIM. Collectively, our results indicate that SIM inhibits cell proliferation and arrests NCI-H460 cell cycle progression via inhibition of cyclin-dependent kinases and cyclins and the enhancement of CDK inhibitors p16 and p27. Our findings suggest that, in addition to the known effects on hypercholesterolemia therapy, SIM may also provide antitumor activity in established NSCLC.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.