Energy balance modulation and pancreatic tumor growth : the role of NF-kB

Abstract

Obesity is a known risk factor for many types of cancer including pancreatic. Calorie restriction (CR), an anti-obesity diet regimen, has potent anticancer effects that may be mediated through its ability to reduce serum metabolic hormones and protumorigenic cytokines such as insulin-like growth factor (IGF)-1. IGF-1 is a metabolic hormone responsive to nutrient status that activates the inflammatory, cancer-related pathway, nuclear factor (NF)-[kappa]B. For this report, we tested the hypothesis that CR, via regulation of IGF-1, inhibits pancreatic tumor cell growth through modulation of NF-kB activation and protumorigenic gene expression. Male athymic nude mice were randomized to either a control diet consumed ad libitum (n=15) or a 30% CR diet (n=15) for 17 weeks, at which time, mice were injected with human pancreatic cancer cells (MiaPaca) and tumor growth was monitored for 6 weeks. Translocation of p65, a regulatory element of NF-[kappa]B, and expression of its downstream gene targets were analyzed in excised tumors. CR mice weighed less, (p<0.05), and had smaller tumors (p=0.022) relative to controls. Tumors from CR mice, relative to controls, demonstrated significant decreases in NF-[kappa]B downstream genes CCND1, RELA, Survivin, VEGF, and XIAP. These findings parallel our previous studies in pancreatic tumors from mouse origin, and suggest that the inhibitory effects of CR on MiaPaca pancreatic tumor growth are associated with decreased NF-kB activation.