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:
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.
Effect of fibroblast growth factor 21 on migration and invasion of human pancreatic cancer cells in an inflammatory environment
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
2
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
2
The expression levels of FGF21 were significantly lower in pancreatic cancer tissues than in normal pancreatic tissues (
P
<
0.05). Compared with LPS-treated cells
the cells treated with both LPS and FGF21 showed significantly lowered migration and invasion abilities (
P
<
0.05) and decreased expression levels of IL-6 and MMP-9 mRNA and MMP-9 protein (
P
<
0.05).
Conclusion
2
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.
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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