Abstract 4428: Metformin effects on ABCB1 expression and proliferation in pancreatic cancer cell lines with different ABCB1 genotypes/haplotypes

Abstract

Abstract Pancreatic cancer carries a poor prognosis and survival rate. Developing effective agents or repurposing agents with low toxicity, such as metformin, an insulin-lowering drug, has recently been investigated for pancreatic cancer. Metformin has long been associated with decreased cancer risk, particularly in diabetic patients. Although its major action is inhibiting hepatic glucose production, it also improves insulin sensitivity in peripheral tissues. This study demonstrates that metformin modulates the ATP-binding cassette gene, ABCB1, expression in pancreatic cancer cell lines with different ABCB1 genotypes. Metformin (100μM or 200μM) alone (p = 0.0212 or p = 0.0161) or in combination with gemcitabine (15nM) (p = 0.0248 or p = 0.0174) significantly decreased ABCB1 expression in Mia pancreatic cells after 24 hr and/or 72 hr treatments. This correlated to increased cell death. Metformin in combination with indole-3-carbinol also significantly (p = 0.0317) decreased ABCB1 expression. However, a sex or genotype difference was noted when two female pancreatic cell lines, SU86.86 and AsPC1, were used. Metformin did not down-regulate ABCB1 expression and was chemoresistance in these two cell lines. AsPC1 and SU86.86 both carry the 2677GG-3435CC ABCB1 haplotype compared to MiaPaca-2 which carries the 2677TT-3134TT ABCB1 haplotype. The 2677TT and 3435TT genotypes/haplotypes are known to be associated with lower risk of developing pancreatic cancer but these data demonstrate that these genotypes are also more sensitive to metformin treatment compared to the 2677GG or 3435CC genotypes. Further research is needed to ascertain whether sex or genotype is contributing to different efficacy of metformin in pancreatic cancer cells with different genotypes. Citation Format: Beverly D. Lyn-Cook, Taylor Osborne, Stancy Joseph, Beverly Word, Li Pang, George Hammons. Metformin effects on ABCB1 expression and proliferation in pancreatic cancer cell lines with different ABCB1 genotypes/haplotypes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4428. doi:10.1158/1538-7445.AM2015-4428