Wang Zhenshi, Zhang Lanyue, Wan Zheng, He Yan, Huang Huarong, Xiang Hongping, Wu Xiaofeng, Zhang Kun, Liu Yang, Goodin Susan, Du Zhiyun, Zheng Xi
Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China.
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Pathol Oncol Res. 2020 Jan;26(1):209-216. doi: 10.1007/s12253-018-0415-7. Epub 2018 May 24.
Atorvastatin is the most prescribed cholesterol-lowering statin, while caffeine enhances chemo-sensitivity and induces apoptosis of tumor cells through its DNA repair-inhibiting effect. The present study investigated the effects and mechanisms of atorvastatin and caffeine in combination on human prostate cancer cells cultured in vitro. Cell growth were determined by the trypan blue exclusion assay. The cell apoptosis and colony formation were determined by morphological assessment. The ability of cell migration and invasion were performed using a scratch wound-healing and Transwell assay. Tumorspheres were formed in suspension under the condition of non-adherence and serum-free medium. Finally, the western blot assay was used to determine the levels of proteins. The combination synergistically suppressed proliferation and induced apoptotic death. Meanwhile, the migration, invasion, and the formation of tumorspheres were significantly inhibited by the combination. We found that atorvastatin and caffeine in combination downregulated phospho-Akt, phospho-Erk1/2, anti-apoptotic Bcl-2 and Survivin protein levels. Results of the present study indicate treatment with the combination of caffeine and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically.
阿托伐他汀是处方量最多的降胆固醇他汀类药物，而咖啡因可增强化疗敏感性并通过其抑制DNA修复的作用诱导肿瘤细胞凋亡。本研究调查了阿托伐他汀和咖啡因联合使用对体外培养的人前列腺癌细胞的影响及其机制。通过台盼蓝排斥试验测定细胞生长情况。通过形态学评估确定细胞凋亡和集落形成。使用划痕伤口愈合试验和Transwell试验检测细胞迁移和侵袭能力。在非贴壁和无血清培养基条件下悬浮形成肿瘤球。最后，使用蛋白质印迹法测定蛋白质水平。联合用药协同抑制增殖并诱导凋亡性死亡。同时，联合用药显著抑制了迁移、侵袭以及肿瘤球的形成。我们发现阿托伐他汀和咖啡因联合使用可下调磷酸化Akt、磷酸化Erk1/2、抗凋亡Bcl-2和Survivin蛋白水平。本研究结果表明，咖啡因和阿托伐他汀联合治疗可能是抑制前列腺癌生长的有效策略，应进行临床评估。
