成纤维细胞生长因子21对炎症环境下人胰腺癌细胞迁移和侵袭的影响

肖维; 朱莎莎; 郑磐淳; 杨雅莹

doi:10.16016/j.1000-5404.201909197

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成纤维细胞生长因子21对炎症环境下人胰腺癌细胞迁移和侵袭的影响

基础医学 | 更新时间：2026-01-09

- 成纤维细胞生长因子21对炎症环境下人胰腺癌细胞迁移和侵袭的影响
- Effect of fibroblast growth factor 21 on migration and invasion of human pancreatic cancer cells in an inflammatory environment
- 第三军医大学学报 2020年42卷第4期页码：414-420
- 作者机构：
  
  1.400016 重庆，重庆医科大学:分子医学诊断中心病理教研室
  2.400016 重庆，重庆医科大学:附属第一医院临床分子医学检测中心
- 作者简介：
  
  [杨雅莹，E-mail: yangyaying2003@163.com YANG Yaying, E-mail: yangyaying2003@163.com
- 基金信息：
  
  重庆市教委科学技术研究项目(KJ1702016)
- DOI：10.16016/j.1000-5404.201909197
  中图分类号： R341; R364.5; R735.9
- 收稿：2019-09-26，
  
  修回：2019-12-06，
  
  纸质出版：2020-02-28
- 稿件说明：
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肖维, 朱莎莎, 郑磐淳, 等. 成纤维细胞生长因子21对炎症环境下人胰腺癌细胞迁移和侵袭的影响[J]. 第三军医大学学报, 2020,42(4):414-420.

Wei XIAO, Shasha ZHU, Panchun ZHENG, et al. Effect of fibroblast growth factor 21 on migration and invasion of human pancreatic cancer cells in an inflammatory environment[J]. Journal of Third Military Medical University, 2020, 42(4): 414-420.
肖维, 朱莎莎, 郑磐淳, 等. 成纤维细胞生长因子21对炎症环境下人胰腺癌细胞迁移和侵袭的影响[J]. 第三军医大学学报, 2020,42(4):414-420. DOI： 10.16016/j.1000-5404.201909197.

Wei XIAO, Shasha ZHU, Panchun ZHENG, et al. Effect of fibroblast growth factor 21 on migration and invasion of human pancreatic cancer cells in an inflammatory environment[J]. Journal of Third Military Medical University, 2020, 42(4): 414-420. DOI： 10.16016/j.1000-5404.201909197.

摘要

目的

探讨成纤维细胞生长因子21(fibroblast growth factor 21，FGF21)在胰腺癌中的表达及其对炎症环境下胰腺癌细胞迁移和侵袭的影响。

方法

采用免疫组化检测FGF21在胰腺癌和正常胰腺组织中的表达。将人胰腺癌细胞Capan-1和AsPC-1分为4组:对照组、FGF21组、LPS组和FGF21+LPS组。划痕和Transwell实验检测各组细胞迁移和侵袭能力。RT-qPCR和Western blot分别检测IL-6、MMP-9 mRNA和蛋白的表达。

结果

胰腺癌组织中FGF21表达明显低于正常胰腺组织(

0.05)。与LPS组相比较，FGF21+LPS组细胞的迁移和侵袭能力均显著减弱(

0.05)。RT-qPCR和Western blot结果显示:FGF21+LPS组IL-6、MMP-9 mRNA和MMP-9蛋白表达均显著低于LPS组(

0.05)。

结论

FGF21在胰腺癌组织中呈低表达，FGF21干预后能显著抑制LPS引起的胰腺癌细胞迁移和侵袭能力增高，其机制可能与FGF21抑制IL-6和MMP-9的表达有关。

Abstract

Objective

To investigate the expression of fibroblast growth factor 21 (FGF21) in pancreatic cancer and its effect on migration and invasion of pancreatic cancer cells in an inflammatory environment.

Methods

FGF21 expression was detected in 60 specimens of pancreatic cancer tissues and 55 normal pancreatic tissues using immunohischemistry. Two human pancreatic cancer cell lines (Capan-1 and AsPC-1) were both divided into control group

FGF21 group

lipopolysaccharide (LPS) group and FGF21+LPS group. After corresponding treatment

the cell migration and invasion were evaluated using scratch wound healing assay and Transwell assay. RT-qPCR and Western blotting were used to examine the expression levels of IL-6 and MMP-9 mRNA and MMP-9 protein in the cells.

Results

The expression levels of FGF21 were significantly lower in pancreatic cancer tissues than in normal pancreatic tissues (

0.05). Compared with LPS-treated cells

the cells treated with both LPS and FGF21 showed significantly lowered migration and invasion abilities (

0.05) and decreased expression levels of IL-6 and MMP-9 mRNA and MMP-9 protein (

0.05).

Conclusion

FGF21 expression is significantly decreased in pancreatic cancer tissues. Intervention with FGF21 can significantly inhibit LPS-induced enhancement of migration and invasion of pancreatic cancer cells possibly by inhibiting IL-6 and MMP-9 expression.

关键词

Keywords

references

BRAY F, FERLAY J, SOERJOMATARAM I, et al . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.

RAHIB L, SMITH B D, AIZENBERG R, et al . Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States[J ] . Cancer Res, 2014, 74(11): 2913-2921. DOI: 10.1158/0008-5472.CAN-14-0155.

RYAN D P, HONG T S, BARDEESY N. Pancreatic adenocarcinoma[J]. N Engl J Med, 2014, 371(11): 1039-1049. DOI: 10.1056/nejmra1404198.

KIRKEGÅRD J, MORTENSEN F V, CRONIN-FENTON D. Chronic pancreatitis and pancreatic cancer risk: A systematic review and meta-analysis[J]. Am J Gastroenterol, 2017, 112(9): 1366-1372. DOI: 10.1038/ajg.2017.218.

LIOU G Y, DÖPPLER H, NECELA B, et al . Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-κB and MMPs[J ] . J Cell Biol, 2013, 202(3): 563-577. DOI: 10.1083/jcb.201301001.

HONORATI M C, CATTINI L, FACCHINI A. IL-17, IL-1β and TNF-α stimulate VEGF production by dedifferentiated chondrocytes[J]. Osteoarthr Cartil, 2004, 12(9): 683-691. DOI: 10.1016/j.joca.2004.05.009.

KHARITONENKOV A, ADAMS A C. Inventing new medicines: The FGF21 story[J]. Mol Metab, 2014, 3(3): 221-229. DOI: 10.1016/j.molmet.2013.12.003.

BERGLUND E D, LI C Y, BINA H A, et al . Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity[J ] . Endocrinology, 2009, 150(9): 4084-4093. DOI: 10.1210/en.2009-0221..

SINGHAL G, FISHER F M, CHEE M J, et al . Fibroblast growth factor 21 (FGF21) protects against high fat diet induced inflammation and islet hyperplasia in pancreas[J ] . PLoS ONE, 2016, 11(2): e0148252. DOI: 10.1371/journal.pone.0148252.

GÓMEZ-SÁMANO M Á, GRAJALES-GÓMEZ M, ZUARTH- VÁZQUEZ J M, et al . Fibroblast growth factor 21 and its novel association with oxidative stress[J ] . Redox Biol, 2017, 11: 335-341. DOI: 10.1016/j.redox.2016.12.024.

LUO Y D, YANG YY, LIU M Y, et al . Oncogenic KRAS reduces expression of FGF21 in acinar cells to promote pancreatic tumorigenesis in mice on a high-fat diet[J ] . Gastroenterology, 2019, 157(5): 1413-1428.e11. DOI: 10.1053/j.gastro.2019.07.030.

JOHNSON C L, WESTON J Y, CHADI S A, et al . Fibroblast growth factor 21 reduces the severity of cerulein-induced pancreatitis in mice[J ] . Gastroenterology, 2009, 137(5): 1795-1804. DOI: 10.1053/j.gastro.2009.07.064.

朱莎莎. FGF21对炎症环境下人胰腺癌细胞迁移侵袭的影响及其机制研究[D].重庆: 重庆医科大学, 2019.

ZHU S S. Effect of FGF21 on migration and invasion of human pancreatic cancer cells in inflammatory environment and its possible mechanism[D]. Chongqing: Chongqing Medical Univesity, 2019.

HRUBAN R H, GAIDA MM, THOMPSON E, et al . Why is pancreatic cancer so deadly? The pathologist's view[J ] . J Pathol, 2019, 248(2): 131-141. DOI: 10.1002/path.5260.

DESCHÊNES-SIMARD X, MIZUKAMI Y, BARDEESY N. Macrophages in pancreatic cancer: starting things off on the wrong track[J]. J Cell Biol, 2013, 202(3): 403-405. DOI: 10.1083/jcb.201307066.

LIOU G Y. Inflammatory cytokine signaling during development of pancreatic and prostate cancers[J]. J Immunol Res, 2017, 2017: 7979637. DOI: 10.1155/2017/7979637.

YU Y H, LI S M, LIU Y N, et al . Fibroblast growth factor 21 (FGF21) ameliorates collagen-induced arthritis through modulating oxidative stress and suppressing nuclear factor-kappa B pathway[J ] . Int Immunopharmacol, 2015, 25(1): 74-82. DOI: 10.1016/j.intimp.2015.01.005.

JOHNSON C L, MEHMOOD R, LAING S W, et al . Silencing of the Fibroblast growth factor 21 gene is an underlying cause of acinar cell injury in mice lacking MIST1[J ] . Am J Physiol Endocrinol Metab, 2014, 306(8): E916-E928. DOI: 10.1152/ajpendo.00559.2013.

IKEBE M, KITAURA Y, NAKAMURA M, et al . Lipopolysaccharide (LPS) increases the invasive ability of pancreatic cancer cells through the TLR4/MyD88 signaling pathway[J ] . J Surg Oncol, 2009, 100(8): 725-731. DOI: 10.1002/jso.21392.

KHURANA A, SIKHA M S, RAMESH K, et al . Modulation of cerulein-induced pancreatic inflammation by hydroalcoholic extract of curry leaf (Murraya koenigii)[J ] . Phytother Res, 2019, 33(5): 1510-1525. DOI: 10.1002/ptr.6344.

SONG J K, ZHANG W, WANG J H, et al . Activation of Nrf2 signaling by salvianolic acid C attenuates NF-κB mediated inflammatory response both in vivo and in vitro [J ] . Int Immunopharmacol, 2018, 63: 299-310. DOI: 10.1016/j.intimp.2018.08.004..

ROY R, YANG J, MOSES M A. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer[J]. J Clin Oncol, 2009, 27(31): 5287-5297. DOI: 10.1200/JCO.2009.23.5556.

LESINA M, WÖRMANN S M, NEUHÖFER P, et al . Interleukin-6 in inflammatory and malignant diseases of the pancreas[J ] . Semin Immunol, 2014, 26(1): 80-87. DOI: 10.1016/j.smim.2014.01.002.

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