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作 者:Juan-Juan Shi Yi-Kai Wang Mu-Qi Wang Jiang Deng Ning Gao Mei Li Ya-Ping Li Xin Zhang Xiao-Li Jia Xiong-Tao Liu Shuang-Suo Dang Wen-Jun Wang
机构地区:[1]Department of Infectious Diseases,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi'an 710004,Shaanxi Province,China [2]Department of Operating Room,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi'an 710004,Shaanxi Province,China
出 处:《World Journal of Gastrointestinal Oncology》2024年第2期398-413,共16页世界胃肠肿瘤学杂志(英文版)(电子版)
基 金:the Key Research and Development Program of Shaanxi,No.2021SF-227 and No.2020SF-297;the Natural Science Basic Research Program of Shaanxi,No.2023-JC-YB-770。
摘 要:BACKGROUND Prohibitin 1(PHB1)has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed,and it participates in a variety of essential cellular functions,including apoptosis,cell cycle regulation,prolifera-tion,and survival.Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma(HCC).However,the role of PHB1 in HCC is controversial.AIM To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro.METHODS HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria;then,PHB1 levels in the sera and liver tissues of these participates were determined using ELISA,RT-PCR,and immunohistoche-mistry.Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA(shRNA-PHB1)for 24-72 h.Cell prolif-eration was analysed with an MTT assay.Cell cycle progression and apoptosis were analysed using flow cytometry(FACS).The mRNA and protein expression levels of the cell cycle-related molecules p21,Cyclin A2,Cyclin E1,and CDK2 and the cell apoptosis-related molecules cytochrome C(Cyt C),p53,Bcl-2,Bax,caspase 3,and caspase 9 were measured by real-time PCR and Western blot,respectively.RESULTS Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals,and decreased PHB1 was positively correlated with low differentiation,TNM stage III-IV,and alpha-fetoprotein≥400μg/L.Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner.FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis.The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-tr
关 键 词:Prohibitin 1 Hepatocellular carcinoma cells APOPTOSIS Cell cycle Mitochondrial pathway
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