Therapeutic effects of statins against lung adenocarcinoma via p53 mutant-mediated apoptosis
Therapeutic effects of statins against lung adenocarcinoma via p53 mutant-mediated apoptosis
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DOI：
10.1038/s41598-019-56532-6
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发表时间：
2019-12-31
影响因子：
4.6
通讯作者：
Sher, Yuh-Pyng
中科院分区：
文献类型：
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作者：
Chou, Cheng-Wei;Lin, Ching-Heng;Sher, Yuh-Pyng
p53基因是一个重要的肿瘤抑制基因。突变的p53基因占所有肺癌病例的一半左右。越来越多的证据表明他汀类药物通过抑制甲羟戊酸途径发挥抗肿瘤作用。我们使用台湾全民健康保险研究数据库，回顾性调查他汀类药物使用与肺癌预后的相关性，主要集中在早期肺癌。这项研究报告了他汀类药物对早期肺癌患者的保护作用，无论化疗与否。在这项基于人群的研究中，他汀类药物治疗降低了5年死亡率（比值比，0.43; P < 0.001）。辛伐他汀处理的突变型p53肺癌细胞中观察到显著更高水平的细胞凋亡，抑制细胞生长，调节脂筏含量。此外，辛伐他汀增加了caspase依赖性凋亡途径，促进突变型p53蛋白降解，并降低了p53错义突变肺癌细胞的运动活性。这些数据表明，在选定的肺癌患者中使用他汀类药物可能具有临床益处。
The p53 gene is an important tumour suppressor gene. Mutant p53 genes account for about half of all lung cancer cases. There is increasing evidence for the anti-tumour effects of statins via inhibition of the mevalonate pathway. We retrospectively investigated the correlation between statin use and lung cancer prognosis using the Taiwanese National Health Insurance Research Database, mainly focusing on early-stage lung cancer. This study reports the protective effects of statin use in early-stage lung cancer patients regardless of chemotherapy. Statin treatments reduced the 5-year mortality (odds ratio, 0.43; P < 0.001) in this population-based study. Significantly higher levels of cellular apoptosis, inhibited cell growth, and regulated lipid raft content were observed in mutant p53 lung cancer cells treated with simvastatin. Further, simvastatin increased the caspase-dependent apoptotic pathway, promotes mutant p53 protein degradation, and decreased motile activity in lung cancer cells with p53 missense mutations. These data suggest that statin use in selected lung cancer patients may have clinical benefits.