Open Access

ARTICLE

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

XIN LI^1,2,#, WENKAI JIANG^3,#, WANCHENG LI^3,#, SHI DONG³, YAN DU³, HUI ZHANG^1,*, WENCE ZHOU^1,3,*

1 Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, 730000, China
2 The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China
3 The Second Clinical Medical College, Lanzhou University, Lanzhou, 730000, China

* Corresponding Authors: HUI ZHANG. Email: ; WENCE ZHOU. Email:

Oncology Research 2023, 31(4), 505-514. https://doi.org/10.32604/or.2023.026959

Received 06 October 2022; Accepted 07 April 2023; Issue published 25 June 2023

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.

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