The Antitumor Activity of Betulinic Acid-Loaded Nanoliposomes Against Colorectal Cancer In Vitro and In Vivo via Glycolytic and Glutaminolytic Pathways

Abstract

The purpose of this study is to develop betulinic acid loaded nanoliposomes to improve the chemotherapy effect of colorectal cancer. The cellular uptake and anti-tumor effects of betulinic acid loaded nanoliposomes in vitro were characterized and evaluated, and their effects on glycolysis, glutamine decomposition and key anti-cancer targets were analyzed. Moreover, their anticancer efficacy was assessed in vivo. Compared with free betulinic acid in vitro, the cellular uptake and anti-tumor activity of betulinic acid-loaded nanoliposomes were significantly enhanced; these nanoliposomes significantly suppressed the proliferation and glucose uptake of colorectal cancer cells. Mechanistically, the anti-colorectal cancer effect of betulinic acid-loaded nanoliposomes was confirmed by their triggering of cellular apoptosis and regulating the potential glycolytic and glutaminolytic targets and pathways. After tumor proliferation was inhibited and colorectal cancer cells apoptosis, the anticancer effect of betulinic acid loaded nanoliposomes in vivo was significantly enhanced. All in all, betulinic acid loaded nanoliposomes are expected to be an effective drug delivery system for colorectal cancer treatment.