RESUMEN
Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Colangiocarcinoma/tratamiento farmacológico , Evaluación Preclínica de Medicamentos/métodos , Aloinjertos , Animales , Antineoplásicos/uso terapéutico , Berberina/uso terapéutico , Técnicas de Cultivo de Célula , Trasplante de Células/métodos , Colangiocarcinoma/patología , Cricetinae , Medios de Cultivo/química , Modelos Animales de Enfermedad , Masculino , MesocricetusRESUMEN
Thunbergia laurifolia Linn (Rang Chuet) possesses antioxidant and anti-inflammatory properties as well as anticancer activities. The aim of the present study was to evaluate the efficacy of T. laurifolia in reducing inflammation from pathological changes in Syrian hamsters infected with the human liver fluke Opisthorchis viverrini. Hamster groups were also administered N-nitrosodimethylamine (NDMA) and treated with T. laurifolia. Light microscopic observation of histopathological changes, liver function tests for alanine transaminase (ALT) and alkaline phosphatase (ALP) and kidney function tests for blood urea nitrogen (BUN) and creatinine were performed. Antioxidant effects of both fresh and dried Rang Chuet solutions were observed. Analysis of the histopathological changes showed anti-inflammatory properties, both in the case of O. viverrini infection or with NDMA administration, by reducing the aggregation of inflammatory cells surrounding the hepatic bile ducts as indicated by normal serum ALT, ALP, BUN and creatinine levels in treated Syrian hamsters. The present study found that fresh and dried Rang Chuet solutions clearly reduced the inflammatory cells in both O. viverrini-infected and NDMA-administered groups and was correlated with the total antioxidant capacity. These findings suggest that T. laurifolia possesses antioxidant and anti-inflammatory properties and that its application may be useful for prevention of the inflammatory process, one of the risk factors of O. viverrini-associated cholangiocarcinoma (CCA).