Effect of C6Ceramide on chemotoxicity of gemcitabine against chemoresistant pancreatic cell lines.

Abstract

e15286 Background: Pancreatic cancer is a highly chemo-resistant malignancy with 5% overall survival, and limited treatment options with chemotherapy (Gemcitabine) and surgical resection possible in < 20% of patients with post resection survival of only 15-20%. Our studies suggest potential value of C6 Ceramide as a chemo enhancing biologic in therapy of chemoresistant pancreatic cancer. C6 Ceramide is an active sphingomyelin end product that has the major biologic function of inducing apoptosis in cells compromised or damaged by injury or malignancy, and appears to have potential value in therapy of malignancy. We have demonstrated C6 Ceramide inhibition of pro survival (AKT/PI3K/mTOR) and KRAS mutant pathways, which promote pancreatic cancer growth and metastases. Methods: Cell lines obtained from 4 freshly cultured pancreatic cancers, and 3 well established cancer cell lines (ATCC) were cultured in 96 well plates, 4000 cells/well, and were treated at 24 hours with Gemcitabine in 0.9% NaCl (1,2,5,10 ug/...