title: Establishment of an allo-transplantable hamster cholangiocarcinoma cell line and its application for in vivo screening of anti-cancer drugs.
abstract: 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.
authors: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Nattapong
authors: N
authors: Puthdee
authors: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Japan.
authors: Kulthida
authors: K
authors: Vaeteewoottacharn
authors: Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Wunchana
authors: W
authors: Seubwai
authors: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Orasa
authors: O
authors: Wonkchalee
authors: Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
authors: Worasak
authors: W
authors: Kaewkong
authors: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Amornrat
authors: A
authors: Juasook
authors: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Somchai
authors: S
authors: Pinlaor
authors: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Chawalit
authors: C
authors: Pairojkul
authors: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Chaisiri
authors: C
authors: Wongkham
authors: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Japan.
authors: Seiji
authors: S
authors: Okada
authors: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Thidarut
authors: T
authors: Boonmars
authors: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. ; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors: Sopit
authors: S
authors: Wongkham
mesh_terms: D064591:Allografts; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000627:therapeutic use; D001599:Berberine / Q000627:therapeutic use; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D017690:Cell Transplantation / Q000379:methods; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D006224:Cricetinae; D003470:Culture Media / Q000737:chemistry; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008297:Male; D008647:Mesocricetus
chemical_list: D000970:Antineoplastic Agents; D003470:Culture Media; D001599:Berberine
keywords: Opisthorchis viverrini; allograft transplantation; anti-cancer effect; berberine; cholangiocarcinoma; hamster model