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Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice.
He, Jing-kang; Wu, Xiang-sheng; Wang, Yan; Han, Rong; Qin, Zheng-hong; Xie, Yan.
Afiliación
  • He JK; Department of Cardiothoracic Surgery, the First Affiliated Hospital of Soochow University, Suzhou, China.
Acta Pharmacol Sin ; 34(2): 295-300, 2013 Feb.
Article en En | MEDLINE | ID: mdl-23202800
AIM: To investigate the antitumor actions of the Crotalus durissus neurotoxin (crotoxin) on human esophageal carcinoma (Eca-109) cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. METHODS: The growth-inhibitory effect was analyzed in Eca-109 cells using MTT assay. Cell morphology changes in nuclei were observed using Hoechst 33342 staining, while apoptosis and cell cycle distribution were examined by flow cytometry. RT-PCR was used to measure the Bcl-2, p15, and caspase-3 p17 gene expression levels. A tumor transplantation model was established by inoculation of Eca-109 cells were into female Balb/c nude mice. Crotoxin (25, 50, and 100 mg/kg) was subcutaneously injected into the transplanted tumors every 2 d for a total of 10 injections. Tumor size and weight were measured. Bcl-2, p15, and caspase-3 p17 protein expression in transplanted tumors was analyzed using Western blotting. RESULTS: Crotoxin (25, 50, and 100 µg/mL) inhibited the growth of Eca-109 cells in a dose-dependent manner with inhibition rates of 22.9%, 35.8%, and 57.2%, respectively. Hoechst 33342 staining revealed apoptotic cells with pyknotic nuclear chromatin after crotoxin treatment. In Eca-109 cells, crotoxin induced apoptosis and G1 block, significantly upregulated the expression of p15 and caspase-3 p17 genes and downregulated the expression of Bcl-2 gene. Furthermore, crotoxin inhibited the growth of Eca-109 tumors in nude mice in a dose-dependent manner. Western blotting showed that crotoxin increased p15 and caspase-3 p17 protein levels and reduced Bcl-2 protein level in tumor specimens. CONCLUSION: Crotoxin inhibits the growth of Eca-109 cells in vitro via apoptosis induction and G1 block. Local administration of crotoxin inhibits the growth of subcutaneously transplanted Eca-109 cells in nude mice, possibly via increasing p15 and caspase-3 p17 protein expression and reducing Bcl-2 protein expression.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Crotalus / Crotoxina / Esófago Límite: Animals / Female / Humans Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2013 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Crotalus / Crotoxina / Esófago Límite: Animals / Female / Humans Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2013 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos