Abstract 3522: Pre-treatment with FSH enhances the ability of EP-100 to target and destroy human pancreatic cancer cells

Abstract

Abstract The expression of luteinizing hormone releasing hormone (LHRH) receptors by pancreatic cancer cells has been clearly established. We observed that pancreatic cancer cell lines contain different numbers of LHRH receptors (BxPC3>MIAPaCa-2>PANC-1) using relative quantitation of RNA by real time PCR. In an in vitro study, we found that treatment of PANC-1 cells in culture with small amounts (10 or 30 ng/ml) of follicle stimulating hormone (FSH) caused a 3-fold increase in LHRH receptor gene expression. Therefore, we hypothesized that pre-treatment of nude mice bearing PANC-1 tumor xenografts with FSH will increase the number of LHRH receptors which will enhance the ability of the EP-100 (LHRH conjugated lytic peptide) to target and destroy PANC-1 pancreatic cancer cells. Our main objective was to determine in vitro and in vivo if FSH enhances the efficacy of EP-100 in targeting and destroying PANC-1 cells. PANC-1 cells (5000/well) were pretreated with FSH (10 and 30 ng/mL) for 24 h followed by EP-100 (4 and 6 µM) for 24 h in a medium containing 0.2% Dextran charcoal treated serum. MTT cell viability assay results showed that pre-treatment of PANC-1 cells with FSH significantly (P<0.001) enhanced the cytotoxicity of EP-100. PANC-1 tumor xenograft bearing Athymic Balb/C nude mice (n=11) were treated with EP-100 (0.2 and 0.02 mg/kg), iv, once a week for three weeks with or without FSH pre-treatment, sc, (3 mg/kg for three days prior to administering the conjugate). The treatment groups included were baseline (sacrificed at the beginning of treatment), vehicle, FSH alone, EP-100 (0.02 mg/kg) alone, EP-100 (0.02mg/kg) with FSH, EP-100 (0.2 mg/kg) alone, EP-100 (0.2 mg/kg) with FSH. FSH pre-treatment significantly enhanced the ability of EP-100 (0.02 mg/kg – P<0.05 and 0.2 mg/kg – P<0.001 compared to baseline) to regress the growth of PANC-1 tumor xenografts in vivo. Histopathological evaluation revealed an increase in tumor necrosis in FSH pre-treated mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3522. doi:10.1158/1538-7445.AM2011-3522