Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells
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...
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doaj-71a6ecd9885641ee870a40a945364db22020-11-24T21:45:47ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-07-01157127781279010.3390/ijms150712778ijms150712778Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer CellsWei-Ding Wu0Zhi-Ming Hu1Min-Jie Shang2Da-Jian Zhao3Cheng-Wu Zhang4De-Fei Hong5Dong-Sheng Huang6Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, ChinaGallbladder 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. http://www.mdpi.com/1422-0067/15/7/12778the gallbladder cancercordycepinAMPKmultiple drug resistant (MDR)HIF-1αmTORC1 and chemo-sensitization |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei-Ding Wu Zhi-Ming Hu Min-Jie Shang Da-Jian Zhao Cheng-Wu Zhang De-Fei Hong Dong-Sheng Huang |
spellingShingle |
Wei-Ding Wu Zhi-Ming Hu Min-Jie Shang Da-Jian Zhao Cheng-Wu Zhang De-Fei Hong Dong-Sheng Huang Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells International Journal of Molecular Sciences the gallbladder cancer cordycepin AMPK multiple drug resistant (MDR) HIF-1α mTORC1 and chemo-sensitization |
author_facet |
Wei-Ding Wu Zhi-Ming Hu Min-Jie Shang Da-Jian Zhao Cheng-Wu Zhang De-Fei Hong Dong-Sheng Huang |
author_sort |
Wei-Ding Wu |
title |
Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells |
title_short |
Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells |
title_full |
Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells |
title_fullStr |
Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells |
title_full_unstemmed |
Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells |
title_sort |
cordycepin down-regulates multiple drug resistant (mdr)/hif-1α through regulating ampk/mtorc1 signaling in gbc-sd gallbladder cancer cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2014-07-01 |
description |
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. |
topic |
the gallbladder cancer cordycepin AMPK multiple drug resistant (MDR) HIF-1α mTORC1 and chemo-sensitization |
url |
http://www.mdpi.com/1422-0067/15/7/12778 |
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