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

被引:0
作者
Li, Ping [1 ]
Wang, Kaixuan [2 ]
Song, Jian [3 ]
Chen, Zhuang [3 ]
Li, Yongyu [3 ]
Chen, Zhaowei [1 ]
机构
[1] Hainan Canc Hosp, Digest Endoscopy Ctr, Haikou 570100, Hainan, Peoples R China
[2] Naval Mil Med Univ, Changhai Hosp, Dept Gastroenterol, Shanghai 200433, Peoples R China
[3] Hainan Canc Hosp, Dept Gastroenterol, Haikou 570100, Hainan, Peoples R China
关键词
Pancreatic cancer; THBS1; JAK2/STAT3; Colivelin; Tumor growth; CELLS; THROMBOSPONDIN-1; RESISTANCE; PROMOTES;
D O I
10.1016/j.mcp.2024.102003
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 (R) 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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页数:8
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