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There is increasing evidence that cordycepin can work synergistically with other chemotherapy drugs. Therefore, we investigated whether combination therapy of cordycepin and cDDP may enhance the therapeutic effect of cDDP. We performed a series of functional tests to study the effect of medical treatment on esophageal cancer cells. We then used GO analysis to examine the pathways affected by treatment with cordycepin and cDDP. Next, we observed changes in the abundance of the selected pathway proteins. The in vivo animal model supported the results of the in vitro experiments. Co-treatment with cordycepin and cDDP inhibited cell growth, migration, and metastasis, as well as induced apoptosis. Cordycepin was found to effectively enhance activation of AMPK and inhibited activity of AKT. In all treatment groups, the expression levels of p-PI3K, p-Akt, p-p70S6K, Caspase-3, and Bcl-2 were significantly reduced, while the expression levels of p-AMPK, cleaved Caspase-3, and Bax increased, and the total levels of Akt, PI3K, and p70S6K levels remained unchanged. Overall, cordycepin was found to enhance the chemical sensitivity of esophageal cancer cells to cisplatin by inducing AMPK activation and inhibiting the AKT signaling pathway. Combination therapy of cordycepin and cisplatin represent a novel potential treatment of esophageal cancer.<\/jats:p>","DOI":"10.1038\/s41419-020-03079-4","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T04:03:45Z","timestamp":1602821025000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Cordycepin enhances the chemosensitivity of esophageal cancer cells to cisplatin by inducing the activation of AMPK and suppressing the AKT signaling pathway"],"prefix":"10.1038","volume":"11","author":[{"given":"Ying","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan-Lei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou-san","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Fang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Zhong","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Xing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"3079_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21551","volume":"69","author":"RL Siegel","year":"2019","unstructured":"Siegel, R. 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All animal studies were performed with approval from the Institutional Animal Care and Use Committee of Sun Yat-Sen University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that they have no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"866"}}