title: Involvement of RhoGDI2 in the resistance of colon cancer cells to 5-fluorouracil.
abstract: OBJECTIVE
  The acquisition of resistance to 5-FU is one of the most prominent obstacles to successful chemotherapy, and the mechanisms underlying the resistance are not fully understood. The aim of this study is to identify novel mediators of 5-FU resistance in colon cancer cells.
  
  
  METHODS
  LoVo colon cancer cells were induced to 5-FU resistance in vitro. The global protein profiles between LoVo and its 5-FU resistant derivative cell line LoVo/5-FU were analyzed by two dimensional gel electrophoresis-based comparative proteomics. The identified proteins expression was confirmed by Western blot analysis. The cytotoxicity of 5-FU was measured in LoVo/5-FU after knockdown of RhoGDI2 (one of the identified protien).
  
  
  RESULTS
  Three differentially expressed proteins were identified. RhoGDI2 and CapG were upregulated, whereas proapoptotic protein Maspin was down-regulated in LoVo/5-FU and validated by Western blotting. Furthermore, knockdown of RhoGDI2 expression by transfection with the RhoGDI2-specific siRNA significantly reduced the resistance to 5-FU in LoVo/5-FU (p < 0.05).
  
  
  CONCLUSIONS
  These novel data suggest that these differentially expressed proteins may contribute to the development of 5-FU resistance in colon cancer cells.
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Jianfang
authors.initials: J
authors.lastname: Li
authors.forename: Xiangyi
authors.initials: X
authors.lastname: He
authors.forename: Xuehua
authors.initials: X
authors.lastname: Chen
authors.forename: Beiqin
authors.initials: B
authors.lastname: Yu
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.forename: Jianian
authors.initials: J
authors.lastname: Zhang
authors.forename: Tingfeng
authors.initials: T
authors.lastname: Wang
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Gu
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: C569658:ARHGDIB protein, human; D000964:Antimetabolites, Antineoplastic; D020730:Guanine Nucleotide Dissociation Inhibitors; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D005472:Fluorouracil