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Recent studies emphasize anisomycin as a promising anti\u2010cancer drug candidate. In this work, we systematically investigated the efficacy of anisomycin alone and its combination with the standard\u2010of\u2010care drugs in NSCLC. We showed that anisomycin inhibited growth, migration, and survival in NSCLC cells regardless of genetic mutation status, and to a greater extent than in normal lung epithelial cells. Isobologram analysis showed that the combination of anisomycin with cisplatin, paclitaxel, or gefitinib was synergistic in NSCLC but not normal lung cells. We further demonstrated that anisomycin inhibited NSCLC growth in mice. The combination of anisomycin with cisplatin was more effective than cisplatin alone and completely arrested NSCLC growth throughout the whole duration of treatment. JNK and p38 MAPK were not required for anisomycin\u2019s action. In contrast, anisomycin inhibits PI3K\/Akt\/mTOR pathway. Overexpression of constitutively active Akt reversed the pro\u2010apoptotic effect of anisomycin. Our work demonstrates the selective anti\u2010NSCLC activity of anisomycin via suppressing PI3K\/Akt\/mTOR. Our findings provide preclinical evidence to initialize the clinical trial of using anisomycin to sensitize NSCLC to current therapy.<\/jats:p>","DOI":"10.1111\/fcp.12641","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T15:44:25Z","timestamp":1608306265000},"page":"822-831","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Anisomycin sensitizes non\u2010small\u2010cell lung cancer cells to chemotherapeutic agents and epidermal growth factor receptor inhibitor via suppressing PI3K\/Akt\/mTOR"],"prefix":"10.1111","volume":"35","author":[{"given":"Hongxia","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Zhongnan Hospital of Wuhan University  169 Donghu Rd, Wuchang District Wuhan Hubei 430071 China"},{"name":"Department of Respiratory and Critical Care Medicine The Second Clinical Medical College Yangtze University  1 Nanhuan Road Jingzhou Hubei 434000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Jingzhou Central Hospital The Second Clinical Medical College Yangtze University  1 Nanhuan Road Jingzhou Hubei 434000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Second Clinical Medical College Yangtze University  1 Nanhuan Road Jingzhou Hubei 434000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanbing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Second Clinical Medical College Yangtze University  1 Nanhuan Road Jingzhou Hubei 434000 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