Betulinic acid-mediating miRNA-365 inhibited the progression of pancreatic cancer

Abstract

Background The 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. Methods A rat model and two cell models of pancreatic cancer were established, and the effect of BA on pancreatic cancer was verified in vivo and in vitro by 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. Results BA can significantly inhibit the proliferation and invasion of pancreatic cancer cells and promote apoptosis. In vivo experiments, 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. Conclusion BA 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.

Gypsogenin Battling for a Front Position in the Pentacyclic Triterpenes Game of Thrones on Anti-Cancer Therapy: A Critical Review—Dedicated to the Memory of Professor Hanaa M. Rady

“…Glycyrrhetinic acid is another representative of oleanane-type triterpenoids with ubiquitous anti-cancer activities [53][54][55][56][57][58]. Ursolic acid [48,[59][60][61][62], betulinic acid [63][64][65][66][67][68], and celastrol [69][70][71][72], representing ursane, lupane, and friedelane type triterpenoids, respectively, were reported to possess multifaceted anti-cancer properties.…”