THBS1 knockdown suppresses pancreatic cancer progression through JAK2/STAT3 signaling pathway

IF 2.3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS Molecular and Cellular Probes Pub Date : 2025-02-01 DOI:10.1016/j.mcp.2024.102003

Ping Li , Kaixuan Wang , Jian Song , Zhuang Chen , Yongyu Li , Zhaowei Chen

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Abstract

Background

Thrombospondin 1 (THBS1), a secreted protein, is implicated in the progression of numerous cancers, yet its specific contributions to pancreatic cancer (PC) remain underexplored.

Methods

The association between THBS1 levels and prognosis in PC was investigated. Functional experiments in vitro were used to determine the cell functions of siTHBS1 through CCK8 assay for cell proliferation, Muse® Cell Analyzer for apoptosis, and transwell assay for invasion and migration. Colivelin was applied in recovery experiment to investigate the mechanism of THBS1 regulating the JAK2/STAT3 pathway in BXPC-3 cell. In addition, the LV-shTHBS1 lentivirus was used to construct subcutaneous tumors in nude mice to verify the function of THBS1 in vivo.

Results

THBS1 expression was elevated in PC and associated with a poorer prognosis. THBS1 was highly expressed in these PC cells. siTHBS1 repressed cell growth, migration and invasiveness, while promoting apoptosis of BXPC-3 cells. THBS1 suppression also led to a decrease in the phosphorylation of JAK2 and STAT3. JAK2/STAT3 signaling activator (Colivelin) could partially reverse the biological effects. In addition, shTHBS1 can suppress the growth of implanted tumors in nude mice.

Conclusions

THBS1 knockdown suppressed cell proliferation, migration, and invasion while enhanced cell apoptosis through the JAK2/STAT3 signaling pathway.

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THBS1敲低通过JAK2/STAT3信号通路抑制胰腺癌进展

背景：血栓反应蛋白1 （THBS1）是一种分泌蛋白，与许多癌症的进展有关，但其对胰腺癌（PC）的特异性贡献仍未得到充分研究。方法：探讨原发性肝癌患者THBS1水平与预后的关系。体外功能实验通过CCK8法检测细胞增殖，Muse®细胞分析仪检测细胞凋亡，transwell法检测细胞侵袭和迁移，检测siTHBS1的细胞功能。利用Colivelin进行恢复实验，探讨THBS1调控BXPC-3细胞JAK2/STAT3通路的机制。此外，我们利用LV-shTHBS1慢病毒在裸鼠体内构建皮下肿瘤，验证THBS1在体内的功能。结果：THBS1在PC中表达升高，预后较差。THBS1在这些PC细胞中高表达。siTHBS1抑制BXPC-3细胞的生长、迁移和侵袭，同时促进BXPC-3细胞的凋亡。THBS1抑制也导致JAK2和STAT3磷酸化水平降低。JAK2/STAT3信号激活因子Colivelin可以部分逆转生物学效应。此外，shTHBS1还能抑制裸鼠植入式肿瘤的生长。结论：THBS1敲低可通过JAK2/STAT3信号通路抑制细胞增殖、迁移和侵袭，同时增强细胞凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular and Cellular Probes 生物-生化研究方法

CiteScore

6.80

自引率

0.00%

发文量

审稿时长

16 days

期刊介绍： MCP - Advancing biology throughâ€“omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.