Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Respiratory and Critical Care Medicine, The Second Clinical Medical College, Yangtze University, Jingzhou, China.
Department of Respiratory and Critical Care Medicine, The Second Clinical Medical College, Yangtze University, Jingzhou, China.
Biochem Biophys Res Commun. 2020 Aug 27;529(3):519-525. doi: 10.1016/j.bbrc.2020.05.127. Epub 2020 Jul 14.
Although the introduction of immune- and targeted-therapy has improved the clinical response and outcomes, lung cancer remains a therapeutic challenge. Developing new therapeutics is necessary to improve the treatment of lung cancer. Here, we show that ribavirin, a clinically available anti-viral drug, is an attractive candidate for lung cancer treatment. We show that ribavirin is active against a panel of lung cancer cell lines regardless of molecular and cellular heterogeneity. Notably, the effective concentrations of ribavirin are clinically achievable, display minimal toxicity to normal cells and synergistic effect with paclitaxel. Its potent efficacy and synergism with chemotherapy on cancer cell, and minimal toxicity on normal cells are observed in lung xenograft mouse model. Ribavirin is also an angiogenesis inhibitor as it inhibits capillary network formation, growth and survival of human lung tumor-associated endothelial cell (HLT-EC). The mechanism studies demonstrate that ribavirin acts on lung cancer cells via suppressing eIF4E and mTOR signaling, leading to the subsequent inhibition of eIF4E-mediated protein translation. Our work suggests that ribavirin has advantage than many anti-cancer agents by targeting both tumor cells and angiogenesis. Our work also highlights the therapeutic potential of ribavirin for the treatment of lung cancer.
虽然免疫治疗和靶向治疗的引入改善了临床反应和结局，但肺癌仍然是一个治疗挑战。开发新的治疗方法对于改善肺癌的治疗是必要的。在这里，我们表明，利巴韦林，一种临床可用的抗病毒药物，是治疗肺癌的一个有吸引力的候选药物。我们表明，利巴韦林对一组肺癌细胞系具有活性，无论分子和细胞异质性如何。值得注意的是，利巴韦林的有效浓度是临床可达到的，对正常细胞的毒性最小，与紫杉醇具有协同作用。在肺癌异种移植小鼠模型中观察到其对癌细胞的有效疗效和与化疗的协同作用，以及对正常细胞的最小毒性。利巴韦林也是一种血管生成抑制剂，因为它抑制毛细血管网络的形成、生长和人肺癌肿瘤相关内皮细胞（HLT-EC）的存活。机制研究表明，利巴韦林通过抑制 eIF4E 和 mTOR 信号通路作用于肺癌细胞，从而随后抑制 eIF4E 介导的蛋白质翻译。我们的工作表明，利巴韦林通过靶向肿瘤细胞和血管生成具有比许多抗癌药物更有优势。我们的工作还突出了利巴韦林治疗肺癌的治疗潜力。
