Abstract 3545: Alterations of molecular mechanisms in newly selected 5-fluorouracil resistant pancreatic cancer cell line and the effect of biochanin A thereon

Abstract

Abstract Resistance to drugs is one of the major contributor to the high mortality rate of pancreatic cancer. The molecular mechanisms of pancreatic cancer drug resistance are not well understood. We generated and characterized a 5FU resistant pancreatic cancer cell line (AsPC1/R). 5FU resistant pancreatic cancer cells (AsPC1/R) were selected with the increasing concentration of the drug till 6-fold resistance was achieved. Our dose response studies show that the resistant cells were cross-resistant to the gefitinib; however, the sensitivity to gemcitabine was not altered. Western blot analysis shows lower level of EGFR in the AsPC1/R as compared to AsPC1 cells. In addition, our results indicate that the resistant cells have high levels of activated Erk 1 and Akt. Levels of c-fos and c-jun in the nuclear fraction were upregulated in the resistant cells. Furthermore, invasive mechanisms such as uPAR and MMP activity are upregulated in the AsPC1/R cells compared to the parent cells. We also determined the effect of biochanin A on 5FU resistance and found that it reverses the 5FU resistance in AsPC1/R cells. Our previous studies have shown that biochanin A reduces the levels of thymidylate synthase and the levels of activated Erk and Akt. We conclude that biochanin A may overcome 5FU resistance in pancreatic cancer and could be used in combination with other chemotherapeutic agents in treating pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3545.