桦木酸介导的 miRNA-365 抑制胰腺癌的进展。

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

机构信息

Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, 730000, China.

The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China.

出版信息

Oncol Res. 2023 Jun 27;31(4):505-514. doi: 10.32604/or.2023.026959. eCollection 2023.

DOI:10.32604/or.2023.026959

PMID:37415745

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10319593/

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 and 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. experiments, BA can significantly lower the number of cancer cells and tumor volume in the rat model of pancreatic cancer. , 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.

摘要

背景

胰腺癌的治疗困境已成为全球性挑战。为此，目前急需寻找有效、可行的新医疗方法。白桦脂酸（BA）已被视为治疗胰腺癌的潜在药物。然而，BA 抑制胰腺癌发展的作用机制仍不清楚。

方法

建立大鼠胰腺癌模型和两种胰腺癌细胞模型，通过 MTT、Transwell、流式细胞术、RT-PCR、Elisa 和免疫组化验证 BA 对胰腺癌的作用。同时，引入 miR-365 抑制剂，以测试 BA 是否通过调节 miR-365 发挥作用。

结果

BA 可显著抑制胰腺癌细胞的增殖和侵袭，促进细胞凋亡。体内实验表明，BA 可显著降低胰腺癌大鼠模型中癌细胞数量和肿瘤体积。进一步研究发现，BA 通过调节 miR365/BTG2/IL-6 的表达抑制 AKT/STAT3 的蛋白水平和磷酸化水平。与 BA 类似，miR-365 抑制剂也显著抑制细胞活力和侵袭能力，并通过改变 BTG2/IL-6 的表达抑制 AKT/STAT3 的蛋白水平和磷酸化水平，两者联合具有协同作用。