title: Anticancer Effects of a New Aminosugar-conjugated Platinum Complex Agent Against Cisplatin-resistant Gastric Cancer.
abstract: Resistance against cisplatin is a problem for the success of gastric cancer chemotherapy. Herein, we evaluated the antitumor effect of a new aminosugar-conjugated, mono-functional platinum complex (Pt-Oqn), which forms a single covalent bond with DNA.
  
  
  
  We compared the cytotoxicity of Pt-Oqn to that of cisplatin (CDDP), oxaliplatin (L-OHP) and carboplatin (CBDCA). We also compared Pt-Oqn and cisplatin for DNA double-strand breaks based on phosphorylated histone H2AX levels in cancer cells and antitumor effects in xenograft models.
  
  
  
  The resistance factor (RF) for Pt-Oqn was low among the four drugs, indicating the potential of Pt-Oqn for overcoming CDDP-induced resistance. In MKN45-R cells, γ-H2AX protein increased following treatment with Pt-Oqn, but not with cisplatin. Finally, Pt-Oqn, but not cisplatin, showed significant antitumor effects in MKN45-R xenografts.
  
  
  
  This new aminosugar-conjugated platinum complex is a promising candidate agent for overcoming the drug resistance of cisplatin-resistant stomach cancer.
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Noriyuki
authors: N
authors: Hayashi
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan hkataoka@med.nagoya-cu.ac.jp.
authors: Hiromi
authors: H
authors: Kataoka
authors: Graduate School of Materials Science, Nara Institute of Science and Technology, Nara, Japan.|Office of Society-Academia Collaboration for Innovation, Kyoto University, Kyoto, Japan.
authors: Shigenobu
authors: S
authors: Yano
authors: Graduate School of Materials Science, Nara Institute of Science and Technology, Nara, Japan.
authors: Jun-Ichi
authors: JI
authors: Kikuchi
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Mamoru
authors: M
authors: Tanaka
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Hirotada
authors: H
authors: Nishie
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Osaka, Japan.
authors: Yuma
authors: Y
authors: Kinoshita
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Osaka, Japan.
authors: Miki
authors: M
authors: Hatano
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Osaka, Japan.
authors: Akihiro
authors: A
authors: Nomoto
authors: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Osaka, Japan.
authors: Akiya
authors: A
authors: Ogawa
authors: Department of Biochemistry, Osaka Medical Centre for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors: Masahiro
authors: M
authors: Inoue
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Tsutomu
authors: T
authors: Mizoshita
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Takaya
authors: T
authors: Shimura
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Yoshinori
authors: Y
authors: Mori
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Eiji
authors: E
authors: Kubota
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Satoshi
authors: S
authors: Tanida
authors: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Takashi
authors: T
authors: Joh
mesh_terms: D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D017671:Platinum Compounds / Q000737:chemistry / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy*
chemical_list: D017671:Platinum Compounds; D002945:Cisplatin
keywords: Platinum complex; chemotherapy; cisplatin; cisplatin resistance; gastric cancer