Establishment of an Allo-Transplantable Hamster Cholangiocarcinoma Cell Line and Its Application for In Vivo Screening of Anti-Cancer Drugs
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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.
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.
참고문헌 (24)
- Shin HR, "Epidemiology of cholangiocarcinoma : an update focusing on risk factors", Cancer Sci, 101, pp.579~585 (2010)
- Sripa B, "Cholangiocarcinoma : lessons from Thailand", Curr Opin Gastroenterol, 24, pp.349~356 (2008)
- Khan SA, "Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document", Gut, 51(suppl 6), pp.VI1~VI9 (2002)
- Morise Z, "Surgery and chemotherapy for intrahepatic cholangiocarcinoma", World J Hepatol, 2, pp.58~64 (2010)
- Thamavit W, "Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini-infected Syrian golden hamsters", Cancer Res, 38, pp.4634~4639 (1978)
- Boonjaraspinyo S, "Overexpression of PDGFA and its receptor during carcinogenesis of Opisthorchis viverrini-associated cholangiocarcinoma", Parasitol Int, 61, pp.145~150 (2012)
- Prakobwong S, "Curcumin decreases cholangiocarcinogenesis in hamsters by suppressing inflammation-mediated molecular events related to multistep carcinogenesis", Int J Cancer, 129, pp.88~100 (2011)
- Pinlaor S, "Nitrative and oxidative DNA damage in intrahepatic cholangiocarcinoma patients in relation to tumor invasion", World J Gastroenterol, 11, pp.4644~4649 (2005)
- Thanan R, "Urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine in patients with parasite infection and effect of antiparasitic drug in relation to cholangiocarcinogenesis", Cancer Epidemiol Biomarkers Prev, 17, pp.518~524 (2008)
- Boonmars T, "Alterations of gene expression of RB pathway in Opisthorchis viverrini infection-induced cholangiocarcinoma", Parasitol Res, 105, pp.1273~1281 (2009)
- Sawanyawisuth K, "A novel carbohydrate antigen expression during development of Opisthorchis viverrini-associated cholangiocarcinoma in golden hamster : a potential marker for early diagnosis", Parasitol Int, 61, pp.151~154 (2012)
- Silsirivanit A, "A novel serum carbohydrate marker on mucin 5AC : values for diagnostic and prognostic indicators for cholangiocarcinoma", Cancer, 117, pp.3393~3403 (2011)
- Flavell DJ, "Promotion of N-nitrosodimethylamine-initiated bile duct carcinogenesis in the hamster by the human liver fluke, Opisthorchis viverrini", Carcinogenesis, 4, pp.927~930 (1983)
- Seubwai W, "Cepharanthine exerts antitumor activity on cholangiocarcinoma by inhibiting NF-κB", Cancer Sci, 101, pp.1590~1595 (2010)
- Imanshahidi M, "Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine", Phytother Res, 22, pp.999~1012 (2008)
- Tang J, "Berberine and Coptidis rhizoma as novel antineoplastic agents : a review of traditional use and biomedical investigations", J Ethnopharmacol, 126, pp.5~17 (2009)
- Letasiova S, "Berberine-antiproliferative activity in vitro and induction of apoptosis", necrosis of the U937 and B16 cells, 2006, pp.239, 254~262
- Hwang JM, "Berberine induces apoptosis through a mitochondria", caspases pathway in human hepatoma cells, 2006, pp.80, 62~73
- Mantena SK, "Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells", Mol Cancer Ther, 5, pp.296~308 (2006)
- He W, "Berberine inhibits growth and induces G1 arrest and apoptosis in human cholangiocarcinoma QBC939 cells", J Pharmacol Sci, 119, pp.341~348 (2012)
- Kaewkong W, "Chromosomes and karyotype analysis of a liver fluke, Opisthorchis viverrini, by scanning electron microscopy", Parasitol Int, 61, pp.504~507 (2012)
- Tengchaisri T, "Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters", Cancer Lett, 133, pp.169~175 (1998)
- Tengchaisri T, "Establishment and characterization of cell lines from liver fluke-associated cholangiocarcinoma induced in a hamster model", Southeast Asian J Trop Med Public Health, 26, pp.231~239 (1995)
- Jinawath N, "Comparison of gene expression profiles between Opisthorchis viverrini and non-Opisthorchis viverrini associated human intrahepatic cholangiocarcinoma", Hepatology, 44, pp.1025~1038 (2006)