重组人白细胞介素17A对结肠癌细胞生长的影响及其作用机制
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摘要
目的:探讨重组人白细胞介素17A (IL-17A)对结肠癌细胞生长的影响,并阐明其作用机制。方法:将结肠癌SW480细胞分为对照组和实验组,对照组细胞未经处理,实验组细胞加入50μg·L-1重组人IL-17A。采用CKK-8法检测2组SW480细胞增殖活性,采用ELISA法检测2组细胞中IL-17A水平,Western blotting法检测2组SW480细胞中信号传导及转录激活因子3 (STAT3)和磷酸化信号传导及转录激活因子3(p-STAT3)蛋白表达水平。结果:与对照组比较,实验组细胞增殖活性明显升高(P<0.05)。与对照组比较,实验组SW480细胞中IL-17A水平、STAT3和p-STAT3蛋白表达水平明显升高(P<0.01)。结论:重组人IL-17A可刺激结肠癌细胞SW480细胞的生长,其作用机制可能与激活STAT3信号通路有关。
Objective:To explore the effect of recombinant human interleukin-17 AI(IL-17 A)on the growth of colon cancer cells,and to investigate the related mechanism.Methods:The colon cancer SW480 cells were divided into control group and experimental group.The SW480 cells in control group were untreated and the SW480 cells in experimental group were added with 50μg·L-1 IL-17 A.The proliferation abilities of SW480 cells in two groups were detected by CKK-8 method.The levels of IL-17 Ain the SW480 cells in two groups were detected by ELISA,and the expression levels of signal transducers and activators of transcription 3(STAT3)and p-signal transducers and activators of transcriptions 3(p-STAT3)were examined by Western blotting methed.Results:Compared with control group,the proliferation ability of the SW480 cells in experimental group was increased(P<0.05).The level of IL-17 Ain the SW480 cells in experimental group was significantly higher than that in control group(P<0.01).Compared with control group,the expression levels of STAT3 and p-STAT3 proteins in the SW480 cells in experimental group were significantly higher than those in control group(P<0.01).Conclusion:Recombinant protein IL-17 Acan stimulate the growth of colon cancer SW480 cells,which may be related to the activation of STAT3 signaling pathway.
Objective:To explore the effect of recombinant human interleukin-17 AI(IL-17 A)on the growth of colon cancer cells,and to investigate the related mechanism.Methods:The colon cancer SW480 cells were divided into control group and experimental group.The SW480 cells in control group were untreated and the SW480 cells in experimental group were added with 50μg·L-1 IL-17 A.The proliferation abilities of SW480 cells in two groups were detected by CKK-8 method.The levels of IL-17 Ain the SW480 cells in two groups were detected by ELISA,and the expression levels of signal transducers and activators of transcription 3(STAT3)and p-signal transducers and activators of transcriptions 3(p-STAT3)were examined by Western blotting methed.Results:Compared with control group,the proliferation ability of the SW480 cells in experimental group was increased(P<0.05).The level of IL-17 Ain the SW480 cells in experimental group was significantly higher than that in control group(P<0.01).Compared with control group,the expression levels of STAT3 and p-STAT3 proteins in the SW480 cells in experimental group were significantly higher than those in control group(P<0.01).Conclusion:Recombinant protein IL-17 Acan stimulate the growth of colon cancer SW480 cells,which may be related to the activation of STAT3 signaling pathway.
引文
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[15]冯洁琼,冯梅宝,徐芳英.炎症小体与结直肠癌的研究进展[J].中华病理学杂志,2017,46(2):132-135.
[16]李必一,王若雨,赵勇.IL-17在肿瘤发生发展中的作用及其临床意义[J].中国医药生物技术,2016,12(1):64-68.
[17]赵子龙,周国江,任玉峰,等.IL-1β、IL-6、IL-17的表达和HPV感染与宫颈癌的相关性研究[J].实用癌症杂志,2017,32(3):358-360.
[18]杨丽娟,赵莎,张海谱,等.IL-17体内外抗肿瘤作用及其机制研究[J].免疫学杂志,2012,28(9):764-769,775.
[19]魏泰,吴立玲,俞光岩.白介素-17在恶性肿瘤发生发展过程中作用及其机制的研究进展[J].生理科学进展,2016,47(5):335-339.
[20]郑仁东,张会峰,曹琳,等.白细胞介素6对未分化型甲状腺癌肿瘤干细胞增殖的影响[J].中华内分泌代谢杂志,2016,32(10):851-856.
[21]曹洪,罗洁,刘国文,等.姜黄素抑制STAT3磷酸化对乳腺癌细胞增殖及Hsp90α表达的影响[J].临床与实验病理学杂志,2016,32(5):510-513.
[22]焦政,朱国琴,周逸婵,等.熊果酸通过AMPK/STAT3/COX-2信号通路抑制胃癌细胞增殖[J].胃肠病学,2017,22(4):208-213.
[23]王五艺,程勇,万林.AGEs通过JAK2/STAT3信号通路诱导结肠癌SW480细胞增殖、侵袭及上皮间质转化[J].第三军医大学学报,2017,39(24):2390-2395.
[24]李可心,臧梦雅,王冬梅,等.IL-17A对肝癌细胞系干性的影响[J].临床肝胆病杂志,2017,33(6):1131-1136.
[25]杨学良,孙雪梅,赵晓晖,等.IL-17E和IL-17F及其受体在结直肠癌组织中的表达及其意义[J].吉林大学学报:医学版,2018,44(3):574-578.
[26]WU X,YANG T,LIU X,et al.IL-17promotes tumor angiogenesis through Stat3pathway mediated upregulation of VEGF in gastric cancer[J].Tumor Biol,2016,37(4):1-9.
[27]HUANG Q,HAN J,FAN J,et al.IL-17induces EMT via Stat3in lung adenocarcinoma[J].Am J Cancer Res,2016,6(2):440-451.
[2]GONZLEZ N,PRIETO I,DEL PUERTO-NEVADO L,et al.2017update on the relationship between diabetes and colorectal cancer:epidemiology,potential molecular mechanisms and therapeutic implications[J].Oncotarget,2017,8(11):18456.
[3]LIAO Y H,XIA N,ZHOU S F,et al.Interleukin-17Acontributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration[J].Life Sci,2016,149(4):10-17.
[4]GRASER A,EKICI A B,SOPEL N,et al.Rhinovirus inhibits IL-17Aand the downstream immune responses in allergic asthma[J].Mucosal Immunol,2016,9(5):1183-1192.
[5]ZHAO W M,SHAYIMU P,LIU L,et al.Association between IL-17Aand IL-17Fgene polymorphisms and risk of gastric cancer in a Chinese population[J].Genet mol Res,2016,15(3).DOI:10.4238/gmr.15037864.
[6]CHOI W S,KIM O,YOON J H,et al.Association of IL-17A/Fpolymorphisms with the risk of gastritis and gastric cancer in the Korean population[J].Mol Cell Toxicol,2016,12(3):327-336.
[7]王庆生,陆航,陈汉蕊,等.IL-17A通过NF-κB通路介导MMP-2/9表达促进结肠癌SW480细胞迁移和侵袭[J].中国肿瘤生物治疗杂志,2017,24(5):516-520.
[8]BHAT S,GARDI N,HAKE S,et al.Impact of intra-tumoral IL17A and IL32 gene expression on T-cell responses and lymph node status in breast cancer patients[J].J Cancer Res Clin Oncol,2017,143(9):1745-1756.
[9]张蓉,梅红,聂亚红,等.Th17细胞及IL-17在卵巢癌患者外周血中的表达及临床意义[J].中国实验诊断学,2016,20(7):1103-1105.
[10]KIM B,PARK B.Saffron carotenoids inhibit STAT3activation and promote apoptotic progression in IL-6-stimulated liver cancer cells[J].Oncol Rep,2018,39(4):1883-1891.
[11]CHEN S F,ZHANG Z Y,ZHANG J L.Matrine increases the inhibitory effects of afatinib on H1975cells via the IL-6/JAK1/STAT3signaling pathway[J].Mol Med Rep,2017,16(3):2733-2739.
[12]WEI L L,XIONG H F,LI W,et al.Upregulation of IL-6expression in human salivary gland cell line by IL-17 via activation of p38 MAPK,ERK,PI3K/Akt,and NF-κBpathways[J].J Oral Pathol Med,2018,47(9):847-855.
[13]WU J H,GUO J P,CAO Q,et al.Autophagy impacts on oxaliplatin-induced hepatocarcinoma apoptosis via the IL-17/IL-17R-JAK2/STAT3signaling pathway[J].Oncol Lett,2017,3(2):770-776.
[14]马松林,张姮,廖宇圣,等.Wnt3a对结肠癌SW480细胞增殖的影响及作用机制[J].山东医药,2016,56(37):23-25.
[15]冯洁琼,冯梅宝,徐芳英.炎症小体与结直肠癌的研究进展[J].中华病理学杂志,2017,46(2):132-135.
[16]李必一,王若雨,赵勇.IL-17在肿瘤发生发展中的作用及其临床意义[J].中国医药生物技术,2016,12(1):64-68.
[17]赵子龙,周国江,任玉峰,等.IL-1β、IL-6、IL-17的表达和HPV感染与宫颈癌的相关性研究[J].实用癌症杂志,2017,32(3):358-360.
[18]杨丽娟,赵莎,张海谱,等.IL-17体内外抗肿瘤作用及其机制研究[J].免疫学杂志,2012,28(9):764-769,775.
[19]魏泰,吴立玲,俞光岩.白介素-17在恶性肿瘤发生发展过程中作用及其机制的研究进展[J].生理科学进展,2016,47(5):335-339.
[20]郑仁东,张会峰,曹琳,等.白细胞介素6对未分化型甲状腺癌肿瘤干细胞增殖的影响[J].中华内分泌代谢杂志,2016,32(10):851-856.
[21]曹洪,罗洁,刘国文,等.姜黄素抑制STAT3磷酸化对乳腺癌细胞增殖及Hsp90α表达的影响[J].临床与实验病理学杂志,2016,32(5):510-513.
[22]焦政,朱国琴,周逸婵,等.熊果酸通过AMPK/STAT3/COX-2信号通路抑制胃癌细胞增殖[J].胃肠病学,2017,22(4):208-213.
[23]王五艺,程勇,万林.AGEs通过JAK2/STAT3信号通路诱导结肠癌SW480细胞增殖、侵袭及上皮间质转化[J].第三军医大学学报,2017,39(24):2390-2395.
[24]李可心,臧梦雅,王冬梅,等.IL-17A对肝癌细胞系干性的影响[J].临床肝胆病杂志,2017,33(6):1131-1136.
[25]杨学良,孙雪梅,赵晓晖,等.IL-17E和IL-17F及其受体在结直肠癌组织中的表达及其意义[J].吉林大学学报:医学版,2018,44(3):574-578.
[26]WU X,YANG T,LIU X,et al.IL-17promotes tumor angiogenesis through Stat3pathway mediated upregulation of VEGF in gastric cancer[J].Tumor Biol,2016,37(4):1-9.
[27]HUANG Q,HAN J,FAN J,et al.IL-17induces EMT via Stat3in lung adenocarcinoma[J].Am J Cancer Res,2016,6(2):440-451.