AstragalosideII inhibits autophagic flux and enhance chemosensitivity of cisplatin in human cancer cells |
| |
| Affiliation: | 1. Affiliated Hospital of Dalian University, Dalian 116001, PR China;2. The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150001, PR China;1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, 200011, China;2. State Key Laboratory of Quality Research in Chinese Medicine and the Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau;3. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China;4. Department of Obstetrics and Gynecology, and Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Canada;5. Department of Cellular and Molecular Medicine, and Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Canada;6. Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Canada |
| |
| Abstract: | Inhibition of autophagy has been daily served as a promising anti-cancer treatment strategies. AstragalosideII (ASII), a main compound isolated from traditional Chinese medicine Radix Astragali, has been demonstrated to inhibit autophagy and reverse multidrug resistance in human hepatic cancer cells Bel-7402/5-FU. In this study, we inspected the function and mechanisms of ASII and cisplatin on autophagy in human cancer cells, and assessed the effect of ASII on cisplatin-induced apoptosis. We found ASII increased LC3II protein level, p62 protein level and GFP-LC3 puncta accumulation in human cancer cells. Furthermore, we found that ASII downregulated the expression of lysosomal cathepsinB/L (CTSB/L) in EBSS medium and affected the lysosomal acidification. Finally, we demonstrated that cisplatin induced protective autophagy which was involved of PI3K/Akt/mTOR pathway. Moreover, ASII in conjunction with cisplatin significant reduced cell viability, arrested in S phase and increased apoptosis. In conclusion, these findings suggested that ASII served as autophagy inhibitor which restored chemosensitivity of anticancer agent cisplatin and enhanced tumor cell death. |
| |
| Keywords: | AstragalosideII Cisplatin Autophagy Apoptosis Sensitization |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
