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Int. J. Mol. Sci. 2014, 15(7), 12778-12790; doi:10.3390/ijms150712778

Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells

Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, China
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Received: 20 May 2014 / Revised: 13 June 2014 / Accepted: 4 July 2014 / Published: 18 July 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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 1α (HIF-1α) expression through activating of AMP-activated protein kinase (AMPK) signaling in gallbladder cancer GBC-SD cells. Contrarily, AMPKα1-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. View Full-Text
Keywords: the gallbladder cancer; cordycepin; AMPK; multiple drug resistant (MDR); HIF-1α; mTORC1 and chemo-sensitization the gallbladder cancer; cordycepin; AMPK; multiple drug resistant (MDR); HIF-1α; mTORC1 and chemo-sensitization
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Wu, W.-D.; Hu, Z.-M.; Shang, M.-J.; Zhao, D.-J.; Zhang, C.-W.; Hong, D.-F.; Huang, D.-S. Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells. Int. J. Mol. Sci. 2014, 15, 12778-12790.

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