Effects of P-MAPA Immunotherapy Associated with Gemcitabine on Chemically-Induced Pancreatic Cancer in Animal Model: New Therapeutic Perspectives

Abstract

Pancreatic cancer is one of the most aggressive tumors since it accounts for approximately 5% of cancer-related deaths worldwide. Immunotherapy based on compounds capable of acting as toll-like receptor (TLRs) agonists may be a valuable strategy to treat cancer, either alone or in association with prevailing therapies. Thus, P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) has emerged as a likely candidate to treat some cancer types, such as pancreatic cancer (PC). The current study reports the effects of an emerging alternative therapy against PC, which lies in associating P-MAPA immunotherapy with gemcitabine-based chemotherapy to treat PC in murine models. Besides, the study reports the potential mechanisms of action of this new therapeutic association involving the TLR4 signaling pathway. PC chemically induced in animal model based on 7,12-dimethylbenz(a)anthracene carcinogen administered by thermosensitive copolymer effectively induced pancreatic tumors in 100% of the investigated rats. P-MAPA-based immunotherapy application alone has shown histopathological repair in 40% of rats, whereas those only treated with gemcitabine have shown 100% of malignant tumors. P-MAPA/Gemcitabine-associated treatment was highly effective in reducing neoplastic lesion progression and enabling histopathological improvement in 80% of the investigated rats. P-MAPA and P-MAPA/Gemcitabine treatments led to increased TLR4 protein contents, which led to increased interferon signaling pathways and positive antitumor effectiveness due to suppressed abnormal cell proliferation. Thus, it is a possible conclusion that the P-MAPA immunotherapy/gemcitabine association had a positive effect on murine models with PC and that it may be a valuable alternative to treat this tumor type.