title: [Antitumor effect of capsaicin on colorectal carcinoma xenograft in nude mice].
abstract: OBJECTIVE
  To evaluate the effect of capsaicin on nude mice xenografted with colorectal carcinoma cells, and to explore its mechanism of action.
  
  
  METHODS
  A nude mouse model of colorectal cancer was established by subcutaneous inoculation of human colorectal carcinoma HT-29 cells. Terminal deoxynucleotidyl transferase-mediated nicked labeling assay (TUNEL) was undertaken to detect the cell proliferation and apoptosis in the xenograft tissue in nude mice. Immunohistochemical (IHC) staining and Western blot were used to detect the expression of HSP27, Cyt-C and active caspase-3.
  
  
  RESULTS
  The tumor growth of the groups C10 and C20 was significantly slower than that of the group NS. The integrated optical density (IOD) of both the group C5 (2532.14 ± 578.11) and group C10 (6364.03 ± 1137.98) was significantly higher than that of the group NS (760.12 ± 238.05), (P < 0.05). The integrated optical density (IOD) of the group C20 was (15743.96 ± 1855.95), significantly higher than that of the groups C10, C5 and NS (all were P < 0.01). Immunohistochemistry showed that the cytoplasmic expression of HSP27 was strongly positive in the group NS, and significantly reduced with the increasing dose of capsaicin in the treated groups. The expression of active caspase-3 and Cyt-C in the group NS was weakly positive, and was significantly increased with the increasing dose of capsaicin in the groups C5 and C10 (P < 0.05), and the expression of active caspase-3 and Cyt-C of the group C20 was significantly higher than that of the groups C5, C10 and NS (P < 0.01). Western blot analysis showed that both the expressions of HSP27 of the group C5 (0.73 ± 0.05) and the group C10 (0.41 ± 0.03) were significantly lower than that of the group NS (P < 0.05). The expression of HSP27 of the group C20 (0.22 ± 0.06) was significantly lower than that of the groups C5, C10 and NS (P < 0.01). The expressions of active-caspase-3 and Cyt-C in the group C5 were (2.57 ± 0.34) and (2.03 ± 0.38), significantly higher than those of the group NS (P < 0.05). The expressions of active-caspase-3 and Cyt-C in the group C10 were (4.23 ± 0.45) and (3.13 ± 0.44), also significantly higher than those of the group NS (P < 0.05). The expressions of active-caspase-3 and Cyt-C in the group C20 were (5.78 ± 0.48) and (4.92 ± 0.52), significantly higher than those of the group C5, C10 and NS (P < 0.01). TUNEL analysis showed that there was a significant difference of cell apoptosis in comparison of each two groups. The higher dose of capsaicin was used, the more apoptosis was observed.
  
  
  CONCLUSIONS
  Capsaicin can significantly inhibit the tumor growth and induce cell apoptosis in the colorectal carcinoma xenograft in nude mice. Its mechanism of action is possibly related with the down-regulation of HSP27 expression and up-regulation of expression of active caspase-3 and Cyt-C in the colorectal carcinoma xenograft in nude mice.
authors.affiliation: Anorectal Department, the Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325027, China.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Zhu
authors.forename: Wan-le
authors.initials: WL
authors.lastname: Hu
authors.forename: Lin-jun
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Zhi-gao
authors.initials: ZG
authors.lastname: Yu
authors.forename: Chong-jie
authors.initials: CJ
authors.lastname: Huang
authors.forename: Ming-zhe
authors.initials: MZ
authors.lastname: Jiang
authors.forename: Ming-xing
authors.initials: MX
authors.lastname: Teng
authors.forename: Jian-lu
authors.initials: JL
authors.lastname: Liu
authors.forename: Chang-bao
authors.initials: CB
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D019073:HT29 Cells; D006360:Heat-Shock Proteins; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018832:Molecular Chaperones; D009368:Neoplasm Transplantation; D011897:Random Allocation; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003574:Cytochrome c Group; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C505407:CASP3 protein, human; D053148:Caspase 3; D002211:Capsaicin