法尼酯X受体通过负调控基质金属蛋白酶7抑制胰腺癌细胞增殖

doi:10.16352/j.issn.1001-6325.2026.02.0250

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (2): 250-255.doi: 10.16352/j.issn.1001-6325.2026.02.0250

法尼酯X受体通过负调控基质金属蛋白酶7抑制胰腺癌细胞增殖

李志涛¹, 步雪峰¹, 张拥军¹, 孟娜娜^2,3, 夏磊洲^1*

镇江市第一人民医院 1.普外科; 2.眼科,江苏镇江 212002; 3.镇江康复眼科医院眼科, 江苏镇江 212002

收稿日期:2025-04-10 修回日期:2025-06-23 出版日期:2026-02-05 发布日期:2026-01-21
通讯作者: ^* xialeizhou6671@163.com
基金资助:
镇江市社会发展项目(FZ2023062, JC2024033);镇江市第一人民医院博士启动基金(KFB2020005);“白求恩·医学科学研究基金”项目(2023-YJ-119-J-031)

Farnesoid X receptor suppresses pancreatic cancer cell proliferation through negative regulation of matrix metalloproteinase 7

LI Zhitao¹, BU Xuefeng¹, ZHANG Yongjun¹, MENG Nana^2,3, XIA Leizhou^1*

Department of General Surgery; 2. Department of Ophthalmology, Zhenjiang First People's Hospital, Zhenjiang 212002; 3. Department of Ophthalmology, Zhenjiang Rehabitation Eye Hospital, Zhenjiang 212002, China

Received:2025-04-10 Revised:2025-06-23 Online:2026-02-05 Published:2026-01-21
Contact: ^* xialeizhou6671@163.com

摘要/Abstract

摘要： 目的探讨胰腺癌细胞中法尼酯X受体(FXR)与基质金属蛋白酶7(MMP7)表达的相关性,并阐明FXR对胰腺癌细胞增殖的作用。方法通过体外实验(CCK-8、RT-PCR、Western blot)检测FXR对胰腺癌细胞(BxPC-3、PANC-1)增殖及MMP7表达的调控作用。结合GEPIA2数据库分析FXR和MMP7在胰腺癌组织中的表达及预后意义;免疫组化染色在组织水平验证二者表达相关性。结果激活FXR(GW4064)显著抑制胰腺癌细胞增殖(P＜0.05),并下调MMP7的mRNA和蛋白表达(P＜0.001、P＜0.01);抑制FXR(NDB)促进胰腺癌细胞增殖(P＜0.01),并上调MMP7的mRNA和蛋白表达(P＜0.01)。MMP7在胰腺癌组织中高表达(P＜0.05),并且与患者不良预后显著相关(P＜0.05),而FXR对预后的影响无统计学意义。免疫组化(n=16)结果提示FXR与MMP7表达呈负相关(R²=0.536 9)。结论 FXR通过负调控MMP7抑制胰腺癌细胞增殖,提示胆汁酸(BAs)-FXR-MMP7轴可能成为胰腺癌治疗的潜在靶点。

关键词: 法尼酯X受体(FXR), 基质金属蛋白酶7(MMP7), 胰腺癌, 细胞增殖, 靶向治疗

Abstract: Objective To investigate the correlation between the expression of farnesoid X receptor (FXR) and matrix metalloproteinase 7 (MMP7) in pancreatic cancer cells, and to elucidate the role of FXR in regulating pancreatic cancer cell proliferation. Methods The effects of FXR on proliferation and MMP7 expression in pancreatic cancer cells (BxPC-3, PANC-1) were evaluated by in vitro experiments (CCK-8 assay, RT-PCR and Western blot). Bioinformatics analysis using GEPIA2 was performed to assess FXR/MMP7 expression and clinical prognosis in pancreatic cancer tissues, with immunohistochemistry (IHC) validating their correlation. Results FXR activation by GW4064 significantly inhibited pancreatic cancer cell proliferation (P＜0.05) and down-regulated MMP7 mRNA and protein levels (P＜0.01); while FXR inhibition by NDB significantly increased pancreatic cancer cell proliferation (P＜0.01) and upregulated the expression of MMP7 mRNA and protein(P＜0.001,P＜0.01). Bioinformatics analysis indicated that MMP7 was highly expressed in pancreatic adenocarcinoma tissues (P＜0.05), and its high expression was significantly associated with poor patient prognosis (P＜0.05); while no statistically significant association was found between FXR and prognosis. IHC (n=16) suggested an inverse correlation between FXR and MMP7 expression (R²=0.536 9). Conclusions FXR suppresses pancreatic cancer cell proliferation by negatively regulating MMP7, suggesting the BA(bile acid)-FXR-MMP7 axis as a potential therapeutic target.

Key words: pancreatic cancer, Farnesoid X receptor(FXR), matrix metalloproteinase 7(MMP7), cell proliferation, targeted therapy

中图分类号:

R735.9

李志涛, 步雪峰, 张拥军, 孟娜娜, 夏磊洲. 法尼酯X受体通过负调控基质金属蛋白酶7抑制胰腺癌细胞增殖[J]. 基础医学与临床, 2026, 46(2): 250-255.

LI Zhitao, BU Xuefeng, ZHANG Yongjun, MENG Nana, XIA Leizhou. Farnesoid X receptor suppresses pancreatic cancer cell proliferation through negative regulation of matrix metalloproteinase 7[J]. Basic & Clinical Medicine, 2026, 46(2): 250-255.

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法尼酯X受体通过负调控基质金属蛋白酶7抑制胰腺癌细胞增殖

Farnesoid X receptor suppresses pancreatic cancer cell proliferation through negative regulation of matrix metalloproteinase 7

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