Department of Thoracic Surgery, Yuhuangding Hospital, Yantai, Shandong, China.
Oncol Res. 2013;20(8):351-7. doi: 10.3727/096504013X13657689382897.
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.
肺癌是最常见的恶性肿瘤之一。近年来，有文献报道他汀类药物具有抗癌和癌症化学预防作用。然而，辛伐他汀对肺癌的作用机制尚不清楚。在本研究中，用人肺癌细胞系 A549 细胞与辛伐他汀孵育。辛伐他汀呈剂量依赖性抑制 A549 细胞的存活，降低 Bcl-2 蛋白表达，增加 Bax 蛋白表达时间和剂量依赖性。此外，辛伐他汀通过增加 caspase-3、-8 和 -9mRNA 和蛋白表达，下调 Xiaps 水平诱导细胞凋亡，阻断细胞周期 G1 期。重要的是，辛伐他汀抑制 MMP-9 蛋白表达的降低并抑制 NF-κB 在 A549 细胞中的激活。综上所述，这些结果表明辛伐他汀通过抑制细胞增殖、影响细胞周期、下调细胞周期蛋白 D1 和 CDK 表达、诱导细胞凋亡和降低 MMP-9 水平，对肺癌 A549 细胞发挥抗癌作用，可能通过抑制 NF-κB 的激活。他汀类药物有助于肺癌的治疗，可能是肺癌的理想抗癌和癌症化学预防药物。
