BackgroundThe dilemma of pancreatic cancer treatment has become a global challenge. For this reason, effective, feasible, and new medical methods are currently much-needed. Betulinic acid (BA) has been valued as a potential therapy for pancreatic cancer. However, the mechanism by which BA exerts an inhibitory effect on the development of pancreatic cancer remains elusive.MethodsA rat model and two cell models of pancreatic cancer were established, and the effect of BA on pancreatic cancer was verifiedin vivoandin vitroby using MTT, Transwell, flow cytometry, RT-PCR, Elisa and immunohistochemistry. At the same time, miR-365 inhibitors were introduced to test whether BA played a role in mediating miR-365.ResultsBA can significantly inhibit the proliferation and invasion of pancreatic cancer cells and promote apoptosis.In vivoexperiments, BA can significantly lower the number of cancer cells and tumor volume in the rat model of pancreatic cancer.In vitro, it was found that BA inhibited the protein level and phosphorylation level of AKT/STAT3 by mediating the expression of miR365/BTG2/IL-6. Like BA, miR-365 inhibitors also significantly inhibited cell viability and invasion ability, and inhibited the protein level and phosphorylation level of AKT/STAT3 by changing the expression of BTG2/IL-6, and their combination had a synergistic effect.ConclusionBA inhibits AKT/STAT3 expression and phosphorylation by modulating miR-365/BTG2/IL-6 expression, and BA inhibits the progression of pancreatic cancer through the aforementioned mechanism.