{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:04:43Z","timestamp":1791601483052,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2014,7,18]],"date-time":"2014-07-18T00:00:00Z","timestamp":1405641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gallbladder cancer is the most common malignancy of the bile duct, with low  5-year survival rate and poor prognosis. Novel effective treatments are urgently needed  for the therapy of this disease. Here, we showed that cordycepin, the bioactive compound in genus Cordyceps, induced growth inhibition and apoptosis in cultured gallbladder  cancer cells (Mz-ChA-1, QBC939 and GBC-SD lines). We found that cordycepin inhibited mTOR complex 1 (mTORC1) activation and down-regulated multiple drug resistant (MDR)\/hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) expression through activating of AMP-activated protein kinase (AMPK) signaling in gallbladder cancer GBC-SD cells. Contrarily, AMPK\u03b11-shRNA depletion dramatically inhibited cordycepin-induced molecular changes as well as GBC-SD cell apoptosis. Further, our results showed that co-treatment with a low concentration cordycepin could remarkably enhance the chemosensitivity of GBC-SD cells to gemcitabine and 5-fluorouracil (5-FU), and the mechanism may be attributed to AMPK activation and MDR degradation. In summary, cordycepin induces growth inhibition and apoptosis in gallbladder cancer cells via activating AMPK signaling. Cordycepin could be a promising new drug or chemo-adjuvant for gallbladder cancer.     <\/jats:p>","DOI":"10.3390\/ijms150712778","type":"journal-article","created":{"date-parts":[[2014,7,18]],"date-time":"2014-07-18T10:30:52Z","timestamp":1405679452000},"page":"12778-12790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Cordycepin Down-Regulates Multiple Drug Resistant (MDR)\/HIF-1\u03b1 through Regulating AMPK\/mTORC1  Signaling in GBC-SD Gallbladder Cancer Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Wei-Ding","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital,  Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Ming","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital,  Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Jie","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital,  Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Jian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital,  Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Wu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital,  Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Fei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital,  Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Sheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital,  Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3322\/caac.21208","article-title":"Cancer statistics, 2014","volume":"64","author":"Siegel","year":"2014","journal-title":"CA Cancer J. 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