title: Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling.
abstract: Sorafenib is a multi-kinase inhibitor applicable to hepatocellular carcinoma (HCC), but its limited therapeutic effects are a major problem to be solved. Here, we show that blockade of ataxia telangiectasia mutated (ATM) improves the antitumor effects of sorafenib. When hepatoma cell lines HepG2 and PLC/PRF/5 were treated with sorafenib plus ATM small inhibitory RNAs, ATM inhibitor KU55933 or caffeine, Akt signaling was suppressed and the cytotoxic effects were significantly potentiated. Moreover, ATM inhibition effectively suppressed the sorafenib-induced cell migration. Taken together, manipulation of ATM activity might be a useful strategy for improving sorafenib treatment of HCC.
authors.affiliation: Department of Medical Technology, Niigata University Graduate School of Health Sciences, Niigata, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Fujimaki
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.forename: Ayumi
authors.initials: A
authors.lastname: Sanpei
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kubota
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagiwa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.forename: Shogo
authors.initials: S
authors.lastname: Ohkoshi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D064007:Ataxia Telangiectasia Mutated Proteins; D001557:Benzenesulfonates / Q000627:therapeutic use*; D002110:Caffeine; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011725:Pyridines / Q000627:therapeutic use*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D010671:Phenylurea Compounds; D011725:Pyridines; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D009536:Niacinamide; D002110:Caffeine; D000077157:Sorafenib; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt