title: Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis.
abstract: Minocycline, a semisynthetic tetracycline, is a highly lipophilic molecule capable of infiltrating tissues and blood. Previous studies have revealed the functions and mechanisms of minocycline in anti-inflammation, protection of the nervous system and certain tumors. The role of minocycline has never been investigated in hepatocellular carcinoma (HCC). The functions of minocycline on HCC cells were investigated using immunohistochemical staining and western blotting. Minocycline was applied to L02, HepG2 and Huh7 cells, and the growth characteristics were studied. Cisplatin was administered in combination with minocycline in this study. Cell cycle and apoptosis analyses were employed to investigate the mechanisms underlying the growth regulation associated with minocycline and(or) cisplatin. Minocycline caused S phase cell cycle arrest and an increase in the apoptotic rate associated with upregulation of p27, cleaved-caspase8, cleaved-caspase3 and cleaved-PRAP-1. Low dose of cisplatin promoted cell cycle arrest and apoptosis, whereas minocycline was mainly associated with upregulation of cleaved-PARP-1. The combination of cisplatin and minocycline increased the rate and extent of cell cycle arrest and increased the apoptosis rate caused by minocycline. A novel mechanism was revealed. Minocycline functions as an antitumor drug in HCC by regulating p27, caspase-3 and PARP-1. Cisplatin enhanced minocycline's effect on PARP-1.
authors.affiliation: Research Laboratory and Hepatic Surgical Center, Department of Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Fu-Yao
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Research Laboratory and Hepatic Surgical Center, Department of Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Research Laboratory and Hepatic Surgical Center, Department of Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Mianyang Center Hospital, Mianyang, Sichuan, P.R. China.
authors.forename: Yue-Ling
authors.initials: YL
authors.lastname: Deng
authors.affiliation: Research Laboratory and Hepatic Surgical Center, Department of Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Zun-Yi
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Research Laboratory and Hepatic Surgical Center, Department of Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Er-Lei
authors.initials: EL
authors.lastname: Zhang
authors.affiliation: Research Laboratory and Hepatic Surgical Center, Department of Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008911:Minocycline / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008911:Minocycline; D002945:Cisplatin