Korean J Parasitol.  2013 Dec;51(6):711-717. 10.3347/kjp.2013.51.6.711.

Establishment of an Allo-Transplantable Hamster Cholangiocarcinoma Cell Line and Its Application for In Vivo Screening of Anti-Cancer Drugs

Affiliations
  • 1Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. kulthidava@kku.ac.th
  • 2Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
  • 3Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
  • 4Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
  • 5Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
  • 6Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
  • 7Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Japan.

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.

Keyword

Opisthorchis viverrini; cholangiocarcinoma; hamster model; allograft transplantation; anti-cancer effect; berberine

MeSH Terms

Allografts
Animals
Antineoplastic Agents/*isolation & purification/therapeutic use
Berberine/therapeutic use
Cell Culture Techniques
*Cell Line, Tumor
Cell Transplantation/methods
Cholangiocarcinoma/*drug therapy/pathology
Cricetinae
Culture Media/chemistry
Disease Models, Animal
Drug Evaluation, Preclinical/*methods
Male
Mesocricetus
Antineoplastic Agents
Berberine
Culture Media
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