title: Inhibitive effects of 15-deoxy-Δ(12),(14)-prostaglandin J2 on hepatoma-cell proliferation through reactive oxygen species-mediated apoptosis.
abstract: OBJECTIVE
  15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) induces reactive oxygen species (ROS)-mediated apoptosis in many malignant cells, which has not been studied in hepatoma cells. In this study, we investigated whether 15d-PGJ2 induced apoptosis in hepatocellular carcinoma (HCC) associated with ROS.
  
  
  METHODS
  The LM3, SMMC-7721, and Huh-7 HCC cell lines were treated with 15d-PGJ2 (5-40 μM) for 24, 48, and 72 hours. Cholecystokinin 8 was used to detect the cytotoxicity of 15d-PGJ2. Flow cytometry, Hoechst staining, and Western blotting were used to analyze apoptosis. ROS were combined with the fluorescent probe dihydroethidium and then observed by fluorescence microscopy and flow cytometry. Activation of JNK and expression of Akt were detected by Western blotting.
  
  
  RESULTS
  15d-PGJ2 inhibited HCC cell proliferation and induced apoptosis in a dose- and time-dependent manner. Apoptosis was mainly induced via an intrinsic pathway and was ROS-dependent, and was alleviated by ROS scavengers. ROS induced JNK activation and Akt downregulation in HCC cells.
  
  
  CONCLUSIONS
  15d-PGJ2 induced ROS in HCC cell lines, and inhibition of cell growth and apoptosis were partly ROS-dependent.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Kan
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Sainan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, First Clinical Medical College of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, First Clinical Medical College of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, First Clinical Medical College of Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Huerxidan
authors.initials: H
authors.lastname: Abudumijiti
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Rongxia
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yingqun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Guo
keywords: 15-deoxy-Δ12,14-prostaglandin J2; JNK; ROS; apoptosis; hepatoma cell