Simvastatin inhibits proliferation and induces apoptosis in human lung cancer cells.
Lung cancer is the one of the most frequent causes of malignant tumors. In recent years, it has been documented that statins have anticancer and cancer chemopreventive properties. However, the mechanism of simvastatin on lung cancer is still unclear. In this study, the human lung cancer cell line A549 cells were incubated with simvastatin. Simvastatin inhibited the survival of A549 cells in a dose-dependent manner, decreased Bcl-2 protein expression, and increased Bax protein expression time and dose dependently. In addition, simvastatin blocked cells in the G1 phase of the cell cycle, downregulated cyclin D1 and CDKs protein expression, mediated the mitochondria-dependent caspase cascade by increasing caspase-3, -8, and -9 mRNA and protein expression, downregulated Xiap levels to induce cells apoptosis. Importantly, simvastatin suppressed decreased MMP-9 protein expression and suppressed NF-κB activation in A549 cells. Taken together, these results showed that the anticancer effect of simvastatin in lung cancer A549 cells via the inhibiting cell proliferation, influencing the cell cycle, downregulating cyclin D1 and CDKs expression, inducing apoptosis, and decreasing MMP-9 levels, possibly by inhibiting the activation of NF-κB. Statins contribute to lung cancer therapy and may be an ideal anticancer and cancer chemopreventive agent for lung cancer.
Department of Thoracic Surgery, Yuhuangding Hospital, Yantai, Shandong, China. Xiaofeng273@yahoo.com.cn
Xiaofeng
X
Yu
Yinghua
Y
Pan
Housheng
H
Ma
Wenjun
W
Li
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D019821:Simvastatin / Q000494:pharmacology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D019821:Simvastatin; D020780:Matrix Metalloproteinase 9