Synergistic antitumor activity of the combination of salubrinal and rapamycin against human cholangiocarcinoma cells
| Autor: | Youping Liu, Jinju Wang, Ying Cheng, Run Chen, Chunyan Duan, Chunhong Feng, Rongyang Dai, Bin Xiao, Hong Li, Fuli Yao, Hong Zhou, Jing Li, Chunyan Zhang, Xiaofang Zhao |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Time Factors Eukaryotic Initiation Factor-2 Salubrinal Cholangiocarcinoma chemistry.chemical_compound 0302 clinical medicine Eukaryotic initiation factor Antineoplastic Combined Chemotherapy Protocols Medicine Phosphorylation Antitumor activity Traditional medicine biology TOR Serine-Threonine Kinases Thiourea Drug Synergism Tumor Burden Oncology 030220 oncology & carcinogenesis Research Paper Signal Transduction bcl-X Protein Mice Nude Bcl-xL 03 medical and health sciences salubrinal In vivo Cell Line Tumor parasitic diseases Animals Humans Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Sirolimus business.industry rapamycin Akt Xenograft Model Antitumor Assays In vitro 030104 developmental biology chemistry Bile Duct Neoplasms Cinnamates biology.protein Cancer research business Proto-Oncogene Proteins c-akt |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Xiaofang Zhao 1, * , Chunyan Zhang 1, * , Hong Zhou 1, * , Bin Xiao 1 , Ying Cheng 1 , Jinju Wang 2 , Fuli Yao 1 , Chunyan Duan 1 , Run Chen 3 , Youping Liu 2 , Chunhong Feng 2 , Hong Li 1 , Jing Li 2 , Rongyang Dai 1 1 Department of Biochemistry and Molecular Biology, Southwest Medical University, Luzhou, Sichuan, China 2 Department of Hepatobiliary Surgery of the Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China 3 Department of Public Health, Southwest Medical University, Luzhou, Sichuan, China * These authors have contributed equally to this work Correspondence to: Rongyang Dai, email: dryrun2502@163.com Jing Li, email: Lijing3107623@aliyun.com Keywords: salubrinal, rapamycin, cholangiocarcinoma, Akt, Bcl-xL Received: August 20, 2016 Accepted: October 27, 2016 Published: November 16, 2016 ABSTRACT Less is known about the roles of eukaryotic initiation factor alpha (eIF2α) in cholangiocarcinoma (CCA). Here, we report that eIF2α inhibitor salubrinal inhibits the proliferation of human CCA cells. Clinical application of mammalian target of rapamycin (mTOR) inhibitors only has moderate antitumor efficacy. Therefore, combination approaches may be required for effective clinical use of mTOR inhibitors. Here, we investigated the efficacy of the combination of salubrinal and rapamycin in the treatment of CCA. Our data demonstrate a synergistic antitumor effect of the combination of salubrinal and rapamycin against CCA cells. Rapamycin significantly inhibits the proliferation of CCA cells. However, rapamycin initiates a negative feedback activation of Akt. Inhibition of Akt by salubrinal potentiates the efficacy of rapamycin both in vitro and in vivo . Additionally, rapamycin treatment results in the up-regulation of Bcl-xL in a xenograft mouse model. It is notable that salubrinal inhibits rapamycin-induced Bcl-xL up-regulation in vivo . Taken together, our data suggest that salubrinal and rapamycin combination might be a new and effective strategy for the treatment of CCA. |
| Databáze: | OpenAIRE |
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