title: [Mechanism of apoptosis of esophageal cancer EC9706 in nude mice induced by all-trans retinoic acid].
abstract: OBJECTIVE
  To investigate the mechanism of apoptosis of EC9706 tumor-bearing nude mice induced by all-trans retinoic acid (ATRA).
  
  
  METHODS
  Human esophageal carcinoma cell line EC9706 cells were inoculated into nude mice to establish the solid tumor model. The tumor models were divided into the following groups: ATRA group, fluorouracil group, the two-drugs combination group, and with an equal volume fraction of solvent as the control group. The nude mice were sacrificed after 10 days of medication. TUNEL staining was used to detect cell apoptosis. RT-PCR was used to detect the expression level of mRNA and immunohistochemistry was used to detect the expression level of protein of caspase-3 and survivin, the apoptosis-related genes in the tumor tissue.
  
  
  RESULTS
  The apoptosis rates of the ATRA group, 5-Fu group and ATRA + 5-Fu group were 44.3%, 39.7% and 91.0%, respectively. There was a significant difference in comparison with the control group (0.7%), and the ATRA group had no significant difference compared with that of the fluorouracil group (P > 0.05), but the apoptosis rate of the two-drugs combination group was significantly higher than that in the two single-drug groups (P < 0.05). The average gray value of caspase-3 protein expressed in the control group was 46.12 ± 0.33 and the relative expression of caspase-3 mRNA was 0.14 ± 0.03, both were significantly lower than that in the ATRA group, 5-Fu group and the two-drugs combination group (P < 0.05). The average gray value of survivin protein expressed in the control group was 96.07 ± 0.13 and the relative expression of survivin mRNA was 0.84 ± 0.04, both were significantly higher than those of other groups (P < 0.05). The ATRA group had no significant difference compared with the fluorouracil group (P > 0.05), but the two-drugs combination group was significantly different compared with the single-drug groups (P < 0.05).
  
  
  CONCLUSIONS
  Apoptosis in the EC9706 tumor cells in nude mice can be induced by ATRA. The mechanism may be related with down-regulation of the level of survivin gene expression and up-regulation of the level of caspase-3 gene expression.
authors.affiliation: Department of Oncology, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Tai-Ying
authors.initials: TY
authors.lastname: Lu
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Li
authors.forename: Xin-Ai
authors.initials: XA
authors.lastname: Wu
authors.forename: Liu-Xing
authors.initials: LX
authors.lastname: Wang
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Wang
authors.forename: Dong-Ling
authors.initials: DL
authors.lastname: Gao
authors.forename: Shi-Xin
authors.initials: SX
authors.lastname: Lu
authors.forename: Qing-Xia
authors.initials: QX
authors.lastname: Fan
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D000077022:Survivin; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin; D014212:Tretinoin; C505407:CASP3 protein, human; D053148:Caspase 3; D005472:Fluorouracil