title: A novel all-trans retinoic acid derivative inhibits proliferation and induces differentiation of human gastric carcinoma xenografts via up-regulating retinoic acid receptor β.
abstract: OBJECTIVE
  This study is to investigate the in vivo effects of 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) on gastric carcinomas (GC).
  
  
  METHODS
  Adult male nude mice were subcutaneously injected with SGC-7901 human gastric cancer cells. Tumor cell cycle was analyzed with flow cytometry. The expression levels of cycloxygenase 2 (COX-2) and carcinoembryonic antigen (CEA) in xenograft tumors were detected with immunohistochemistry. The mRNA and protein expression levels of nuclear retinoic acid receptor β (RARβ) were detected with RT-PCR and Western blot analysis, respectively.
  
  
  RESULTS
  The mean survival time was dramatically increased in the ATPR treatment groups, in a dose-dependent manner. The in vivo results showed that, the xenograft tumor growth was significantly inhibited by the ATPR treatment. Moreover, the percentages of cells in the G0/G1 phase were significantly increased, while the percentages of cells in the S phase were significantly decreased, in the ATPR treatment groups. The serum levels of ALP and LDH were both dramatically decreased in the ATPR treatment groups. Furthermore, immunohistochemistry showed that, the expression levels of COX-2 and CEA were dramatically decreased in the ATPR treatment groups. Importantly, the mRNA and protein expression levels of RARβ in xenograft tumors were apparently increased by the ATPR treatment.
  
  
  CONCLUSIONS
  ATPR could inhibit proliferation and induce differentiation of human gastric carcinoma xenografts via up-regulating RARβ expression. ATPR might be a potential effective antitumor agent for the treatment of GC.
authors.affiliation: College of Pharmacy, Anhui Medical University Hefei, Anhui 230032, China ; Department of Pharmacy, The Anqing Hospital Affiliated to Anhui Medical University Anqing, Anhui 246003, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Pharmacy, The Anqing Hospital Affiliated to Anhui Medical University Anqing, Anhui 246003, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Anhui Medical University Hefei, Anhui 230032, China.
authors.forename: Xinqun
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Anhui Medical University Hefei, Anhui 230032, China.
authors.forename: Feihu
authors.initials: F
authors.lastname: Chen
keywords: 4-amino-2-trifluoromethyl-phenyl retinate (ATPR); antitumor effect; differentiation induction; gastric carcinoma; retinoic acid receptor β (RARβ)