Abstract 5796: Therapeutic effects of statins against lung adenocarcinoma via mutant p53 mediated apoptosis

Abstract

Abstract Introduction The p53 gene is well known as an important tumor suppressor gene. Mutant p53 genes account for about half of all lung cancer cases. There is increasing evidence for the anti-tumor effects of statins via inhibition of the mevalonate pathway. However, the cancer prevention and protection effects of statinsin population-based studies are controversial. Previous population-based studies have shown protective effects of statins in advanced lung cancer patients; however, the effects in early lung cancer patients are unclear. Methods We investigated the correlation between statin use and lung cancer prognosis using the Taiwanese National Health Insurance Research Database retrospectively, mainly focusing on early-stage lung cancer. Cell viability, lipid raft changes, and motile activity from simvastatin-treated cell lines were examined to determine the effect of simvastatin under different p53 mutations. Apoptotic pathways and autophagy in lung cancer cells treated with simvastatin were analyzed using a western blot assay. Results Statin treatments reduced the 5-year mortality (odds ratio, 0.43; 95% confidence interval [CI], 0.37-0.49;P< 0.001) in this population-based study. Simvastatin inhibited cell growth, especially in mutant p53 lung cancer cell lines. Significantly higher levels of cellular apoptosis and decreased lipid rafts were shown in mutant p53 lung cancer cells treated with simvastatin. Further, simvastatin increased activity of the caspase-dependent apoptotic pathway in lung cancer cells containing mutant p53. In addition, simvastatin reduced migration in cells with a mutated p53 gene. Conclusion This study reports the protective effects of statin use in early-stage lung cancer patients regardless of chemotherapy. Simvastatin induced cellular apoptosis and regulated lipid raft content; further, motile activity was reduced in lung cancer cells with p53 missense mutations. These data suggest that statin use in selected lung cancer patients may have clinical benefits. Citation Format: Cheng-wei Chou, Ching-Heng Lin, Tzu-Hung Hsiao, Chia-Chien Lo, Chih-Ying Hsieh, Cheng-Chung Huang, Yuh-Pyng Sher. Therapeutic effects of statins against lung adenocarcinoma via mutant p53 mediated apoptosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5796.