Cun Dongyun, Liu Feng, Tian DaGuang, Li TieHan, Guo ZhaoHao, Chen Peng
Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Kunming Medical University, China.
Department of Hepatobiliary and Pancreatic Surgery, Kunming Medical University, China.
Pathol Res Pract. 2025 Oct;274:156186. doi: 10.1016/j.prp.2025.156186. Epub 2025 Aug 25.
Pancreatic cancer is one of the most aggressive malignant tumors in humans, with poor prognosis. The acetylase tumor inhibitor (Pracinostat) has been shown to suppress the growth of various tumors. This study aimed to investigate the effects of Pracinostat on the pancreatic cancer cell line BxPC3 and to explore the underlying molecular mechanisms through both in vivo and in vitro experiments.
BxPC3 cells were treated with Pracinostat, and cell viability was assessed by CCK-8 assay; the differentially expressed miRNAs in cells before and after pracinostat treatment were screened by high-throughput sequencing, and miR-381-3p was selected as the target gene; the targeting relationship between miR-381-3p and MDM2 was verified by double luciferase reporter gene; the relationship between miR-381-3p, MDM2 and P53 signaling pathways was verified by immunoprecipitation, Western blot and other experiments. Pancreatic tumor models were established in BALB/c nude mice to study the role of pracinostat in vivo.
Pracinostat upregulated the expression of miR-381-3p and p53, while downregulating MDM2 expression. It also inhibited the proliferation and migration of pancreatic cancer cells and promoted apoptosis. Treatment with a miR-381-3p inhibitor reversed the effects of Pracinostat. In addition, MDM2 was found to promote the ubiquitination and degradation of p53 via the ubiquitin-proteasome pathway. In vivo experiments confirmed that Pracinostat inhibited tumor growth in nude mice.
pracinostat activates the p53 signaling pathway by targeting the miR-381-3p/MDM2 axis, thereby inhibiting the proliferation of pancreatic cancer cells. These findings provide novel insights and potential therapeutic strategies for pancreatic cancer, and may also provide a reference for the treatment of other malignancies.
胰腺癌是人类最具侵袭性的恶性肿瘤之一，预后较差。乙酰化酶肿瘤抑制剂（普拉西诺司他）已被证明可抑制多种肿瘤的生长。本研究旨在通过体内和体外实验研究普拉西诺司他对胰腺癌细胞系BxPC3的影响，并探讨其潜在的分子机制。
用普拉西诺司他处理BxPC3细胞，通过CCK-8法评估细胞活力；通过高通量测序筛选普拉西诺司他处理前后细胞中差异表达的miRNA，并选择miR-381-3p作为靶基因；通过双荧光素酶报告基因验证miR-381-3p与MDM2之间的靶向关系；通过免疫沉淀、蛋白质免疫印迹等实验验证miR-381-3p、MDM2与P53信号通路之间的关系。在BALB/c裸鼠中建立胰腺肿瘤模型，研究普拉西诺司他在体内的作用。
普拉西诺司他上调miR-381-3p和p5蛋白的表达，同时下调MDM2的表达。它还抑制胰腺癌细胞的增殖和迁移，并促进细胞凋亡。用miR-381-3p抑制剂处理可逆转普拉西诺司他的作用。此外，发现MDM2通过泛素-蛋白酶体途径促进p53的泛素化和降解。体内实验证实普拉西诺司他可抑制裸鼠肿瘤生长。
普拉西诺司他通过靶向miR-381-3p/MDM2轴激活p53信号通路，从而抑制胰腺癌细胞的增殖。这些发现为胰腺癌提供了新的见解和潜在的治疗策略，也可能为其他恶性肿瘤的治疗提供参考。
