Low-dose LPS and calorie restriction combined therapy for pancreatic ductal adenocarcinoma: an in vitro and in vivo study

Abstract

Objective: This study aimed to evaluate the therapeutic effects of lipopolysaccharide (LPS) on Panc02 cells since LPS is an inflammatory agent with the potential to activate the immune system and reorganize the tumor microenvironment. Moreover, calorie restriction (CR) has been investigated in combination with LPS as a prospective adjuvant intervention for cancer therapy. Materials and Methods: Panc02 cells were cultured in two distinct media with low and high-glucose concentrations, and cell viability was investigated after applying varying doses of LPS to culture media. The in vivo effects of LPS and CR were investigated on the mice subcutaneous pancreatic ductal adenocarcinoma (PDAC) tumor model in terms of tumor mass, histological examination, mRNA expression profiles, and biochemical parameters. Results: The lowest cell count was detected in the cells treated with 10 mu g/ml LPS in low-glucose environments in vivo. Tumor mass significantly decreased in the P+LPS+CR group in vivo. The mRNA expression analysis of tumor tissues indicated that P+LPS+CR acts through NF-kappa B, JNK, and IL-6 signaling pathways. Conclusion: Lipopolysaccharide alone is insufficient to show therapeutic effects, but it can inhibit tumor development by acting on NF-kappa B and JNK pathways when combined with CR. This study gives insight into developing new treatment options for PDAC.