• Annals of surgery · Jun 2002

    Tamoxifen (TMX)/Fas induced growth inhibition of human cholangiocarcinoma (HCC) by gamma interferon (IFN-gamma).

    • Selwyn M Vickers, Nirag C Jhala, Eun-Young Ahn, Jay M McDonald, George Pan, and Kirby I Bland.
    • Department of Surgery, The University of Alabama at Birmingham and Veterans Administration Medical Center, USA. smv@uab.edu
    • Ann. Surg. 2002 Jun 1; 235 (6): 872878872-8.

    ObjectivesTo evaluate the response of human cholangoicarcinoma cells to TMX treatment through the Fas pathway by pretreatment with IFN-gamma.Summary Background DataCholangiocarcinoma remains one of the most difficult tumors to treat in clinical medicine. Currently, there are no effective chemotherapy treatments for this disease. Surgery offers the only opportunity for a cure, with the majority of patients failing to qualify for such treatment. This study seeks to evaluate a potential new modality for treatment of this disease.MethodsHuman cholangiocarcinoma cells were treated with anti Fas mab and sorted to two populations (Fas-positive and Fas-negative) by FAC analysis. In vitro individual cell populations were pretreated with IFN-gamma 250 units/mL x 18hs. The treated cells assayed for caspase 3, 7, 8, Bak, and for apoptosis with Annexin V after treatment with or without TMX. In Vivo 2 x 106 5 SK-ChA-1 Fas-negative cells were injected into nude mice for development of tumor xenografts. Mice received either no treatment or intra tumor IFN-gamma and/or intra peritoneal TMX.ResultsMore than 90% (90% +/- 3.5%) of Fas-positive and 70% (71 +/- 2.3%) of Fas-negative cells underwent apoptosis after TMX treatment when pretreated with IFN-gamma. In contrast, TMX alone and IFN-gamma alone stimulated apoptosis by only 22% (22 +/- 3%) P <.00013, and 17% (17 +/- 2%) P <.0001 in Fas-ve cells respectively. In vivo human cholangiocarcinomas xenograft growth was significantly inhibited by a combination of TMX + IFN-gamma compared to controls P <.0007.ConclusionTMX exposure to human cholangiocarcinoma after pretreatment with IFN-gamma allows for induction of apoptosis in vitro and significant inhibition tumor xenograft growth. The combination of these two compounds may provide novel treatment regimen for cholangiocarcinoma.

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