机构：[1]Department of Chemotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China四川省人民医院四川省肿瘤医院[2]Department of Pharmacy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China临床药学部临床药学部四川省人民医院四川省肿瘤医院[3]Department of Gastroenterology, the Third People’s Hospital of Chengdu, Chengdu, China[4]Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China四川大学华西医院[5]Department of Oncology, Guizhou People’s Hospital, Guizhou, China
The crosstalk between apoptosis and autophagy contributes to tumorigenesis and cancer therapy. The process by which BetA (betulinic acid), a naturally occurring triterpenoid, regulates apoptosis and autophagy as a cancer therapy is unclear. In this study, we show for the first time that protein phosphatase 2A (PP2A) acts as a switch to regulate apoptosis and autophagic cell death mediated by BetA. Under normal conditions, caspase-3 is activated by the mitochondrial pathway upon BetA treatment. Activated caspase-3 cleaves the A subunit of PP2A (PP2A/A), resulting in the association of PP2A and Akt. This association inactivates Akt to initiate apoptosis. Overexpression of Bcl-2 attenuates the mitochondrial apoptosis pathway, resulting in caspase-3 inactivation and the dissociation of PP2A and Akt. PP2A isolated from Akt binds with DAPK to induce autophagic cell death. Meanwhile, in vivo tumor experiments have demonstrated that BetA initiates different types of cell death in a myeloma xenograft model. Thus, PP2A can shift myeloma cells from apoptosis to autophagic cell death. These findings have important implications for the therapeutic application of BetA, particularly against apoptosis-resistant cancers.
基金：
Natural Science Foundation of ChinaNational Natural Science Foundation of China [(NSFC)-81272458]; Program for New Century Excellent Talents in UniversityProgram for New Century Excellent Talents in University (NCET) [(NCET)-12-0381]; Youth Technological Innovation Talent Project Foundation of Sichuan Cancer Hospital
第一作者机构：[1]Department of Chemotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Chemotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China[4]Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
推荐引用方式(GB/T 7714)：
Hang Zhou,Wei Luo,Chao Zeng,et al.PP2A mediates apoptosis or autophagic cell death in multiple myeloma cell lines[J].ONCOTARGET.2017,8(46):80770-80789.doi:10.18632/oncotarget.20415.
APA：
Hang Zhou,Wei Luo,Chao Zeng,Yu Zhang,Liyang Wang...&Chunlai Nie.(2017).PP2A mediates apoptosis or autophagic cell death in multiple myeloma cell lines.ONCOTARGET,8,(46)
MLA：
Hang Zhou,et al."PP2A mediates apoptosis or autophagic cell death in multiple myeloma cell lines".ONCOTARGET 8..46(2017):80770-80789
