[1]冀增秋,顾洪柱,李佳琳,等.基质金属蛋白酶12在胃癌组织、细胞中的表达及对裸鼠移植瘤生长的影响实验研究[J].陕西医学杂志,2024,(6):739-743.[doi:DOI:10.3969/j.issn.1000-7377.2024.06.004]
　JI Zengqiu,GU Hongzhu,LI Jialin,et al.Expression of matrix metalloproteinase-12 in gastric cancer tissues and cells and its effect on growth of transplanted tumor in nude mice[J].,2024,(6):739-743.[doi:DOI:10.3969/j.issn.1000-7377.2024.06.004]
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基质金属蛋白酶12在胃癌组织、细胞中的表达及对裸鼠移植瘤生长的影响实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年6期
页码:
739-743
栏目:
基础研究
出版日期:
2024-06-05

文章信息/Info

Title:
Expression of matrix metalloproteinase-12 in gastric cancer tissues and cells and its effect on growth of transplanted tumor in nude mice
作者:
冀增秋1; 顾洪柱1; 李佳琳2; 王 莹3; 张子玉4
(1.锦州医科大学附属第一医院血管外科,辽宁 锦州 121000; 2.锦州医科大学附属第一医院病理科,辽宁 锦州 121000; 3.锦州医科大学附属第一医院肿瘤科,辽宁 锦州 121000; 4.锦州医科大学附属第一医院健康管理中心,辽宁 锦州 121000)
Author(s):
JI Zengqiu; GU Hongzhu; LI Jialin; WANG Ying; ZHANG Ziyu
(Department of Vascular Surgery,First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China)
关键词:
胃癌;  基质金属蛋白酶12;  增殖细胞核抗原;  裸鼠;  免疫组化;  移植瘤
Keywords:
Gastric cancer;  Matrix metalloproteinase-12;  Proliferating cell nuclear antigen;  Nude mice;  Immunohistochemistry;  Transplanted tumor
分类号:
R 73-3
DOI:
DOI:10.3969/j.issn.1000-7377.2024.06.004
文献标志码:
A
摘要:
目的:观察基质金属蛋白酶12(MMP-12)在胃癌组织和胃癌细胞株SGC-7901中的表达及对裸鼠移植瘤生长的影响。方法:收集胃癌患者42例,手术后留取肿瘤组织和距肿瘤边缘>3 cm的正常胃黏膜组织,应用免疫组化EnVision法检测MMP-12的表达。合成sh-MMP12质粒,应用慢病毒载体转染胃癌细胞株SGC-7901,设为sh-MMP12组,同时设立未行任何干预的细胞为空白对照组(NC组),应用Western blot法检测MMP-12和增殖细胞核抗原(PCNA)蛋白的表达,应用实时荧光定量PCR(RT-qPCR)检测MMP-12和PCNA mRNA的表达。选择4～5周龄的BALB/C雌性裸鼠5只,分别将sh-MMP12组和NC组细胞悬液注射于同一只裸鼠的左右两侧腋下(左侧为sh-MMP12组,右侧为NC组),间隔7 d测量并记录肿瘤体积,28 d后处死小鼠对瘤体称重。结果:免疫组化结果显示,胃癌组织MMP-12阳性率高于正常胃黏膜组织,胃癌组织MMP-12和PCNA表达呈正相关(均P<0.05)。Western blot结果显示,sh-MMP12组MMP-12和PCNA蛋白表达量于NC组(均P<0.05)。RT-qPCR结果显示,sh-MMP12组MMP-12和PCNA mRNA表达量低于NC组(均P<0.05)。裸鼠移植瘤实验结果显示,sh-MMP12组肿瘤体积在7、14 d时与NC组比较无统计学差异(均P>0.05),而在21、28 d时与NC组比较明显缩小(均P<0.05); 28 d后,sh-MMP12组腋下肿瘤重量低于NC组(P<0.05)。结论:胃癌组织和细胞株SGC-7901中MMP-12表达升高,抑制MMP-12可减缓裸鼠移植瘤生长。
Abstract:
Objective:To investigate the expression of matrix metalloproteinase-12(MMP-12)in gastric cancer tissues and gastric cancer cell line SGC-7901 and its effect on the growth of transplanted tumor in nude mice.Methods:Forty-two cases of patients with gastric cancer were collected,and the tumor tissues and normal gastric mucosa tissues(>3 cm from the edge of the tumor)were collected after surgery,and immunohistochemical EnVision method was used to detect the expression of MMP-12.The sh-MMP12 plasmid was synthesized and transfected into SGC-7901 by lentiviral vector,which was set as sh-MMP12 group,and the cells without any intervention were set as blank control group(NC group),and the expressions of MMP-12 and PCNA protein were detected by Western blot,and the expressions of MMP-12 and PCNA mRNA were detected by RT-qPCR.The cell suspension of sh-MMP12 group and NC group were injected into the left and right armpits of 5 BALB/C female nude mice(the left was sh-MMP12 group and the right was NC group),respectively,and the tumor volume was measured and recorded at an interval of 7 days,and the mice were sacrificed after 28 days to weigh the tumor.Results: The results of immunohistochemistry showed that the positive rate of MMP-12 in gastric cancer tissues was higher than that in normal gastric mucosa tissues,and the expression of MMP-12 was positively correlated with PCNA in gastric cancer tissues(all P<0.05).Western blot results showed that the expressions of MMP-12 and PCNA protein in sh-MMP12 group were significantly lower than those in NC group(all P<0.05).RT-qPCR results showed that the expressions of MMP-12 and PCNA mRNA in the sh-MMP12 group were lower than those in the NC group(all P<0.05).The tumor volume of sh-MMP12 group was not significantly different from that of NC group at 7 and 14 days(all P>0.05),but was significantly smaller than that of NC group at 21 and 28 days(all P<0.05); after 28 days,the weight of axillary tumor in sh-MMP12 group was lower than that in NC group(P<0.05).Conclusion:The expression of MMP-12 is increased in gastric cancer tissues and SGC-7901 cell line,and inhibition of MMP-12 can slow down the growth of transplanted tumor in nude mice.

参考文献/References:

[1] 冯璇,寇玉,薛峰,等.半夏泻心汤治疗胃黏膜异型增生疗效及对患者胃癌相关基因甲基化的影响[J].陕西中医,2021,42(8):1020-1023.
[2] 张鑫,田蕾,朱金朋,等.微小RNA-135a-5p和Krüppel样因子16在胃腺癌中的表达及靶向关系研究[J].陕西医学杂志,2022,51(12):1597-1601.
[3] ZHANG S,YANG Y,HUANG S,et al.SIRT1 inhibits gastric cancer proliferation and metastasis via STAT3/MMP-13 signaling[J].J Cell Physiol,2019,234(9):15395-15406.
[4] SAMMARCO G,VARRICCHI G,FERRARO V,et al.Mast cells,angiogenesis and lymphangiogenesis in human gastric cancer[J].Int J Mol Sci,2019,20(9):2106.
[5] 何瑜,唐宽平,马晓颖.5-钙黏蛋白、基质金属蛋白酶9在结直肠癌组织中的表达及临床意义[J].陕西医学杂志,2021,50(5):618-621.
[6] 柳金凤,周厚菊.卵巢癌患者血清MMP12、MMP13水平与临床病理参数和预后的关系[J].中国妇幼保健,2019,34(19):4411-4415.
[7] GOBIN E,BAGWELL K,WAGNER J,et al.A pan-cancer perspective of matrix metalloproteases(MMP)gene expression profile and their diagnostic/prognostic potential[J].BMC Cancer,2019,19(1):581.
[8] LIU A D,PANG J L,XIONG G Y,et al.Forkhead box P4 promotes the proliferation of cells in colorectal adenocarcinoma[J].Oncologie,2023,25(5):543-552.
[9] 刘爱东,张爽,王丹琳,等.MMP-19在胃腺癌中的表达及与神经型钙黏素的相关性[J].重庆医科大学学报,2022,47(2):145-150.
[10] 贾丽.大蒜素对人子宫内膜癌Ishikawa细胞侵袭和迁移抑制作用的研究[J].陕西中医,2020,41(8):1042-1046.
[11] 刘时飞,刘爱东,宋旭东,等.胃腺癌中eIF2α的表达及意义[J].临床与实验病理学杂志,2018,34(6):668-670.
[12] 李向阳,任磊,梁瑞.血清基质金属蛋白酶-9、基质金属蛋白酶-2水平对胃癌腹膜转移及预后的预测价值[J].陕西医学杂志,2023,52(2):166-170.
[13] LI M D,ZHOU L,LI S Y,et al.MMP12 is a potential therapeutic target for adamantinomatous craniopharyngioma:Conclusions from bioinformatics analysis and in vitro experiments[J].Oncology Letters,2021,22(1):5-10.
[14] LIU M,HUANG L,LIU Y,et al.Identification of the MMP family as therapeutic targets and prognostic biomarkers in the microenvironment of head and neck squamous cell carcinoma[J].J Transl Med,2023,21(1):208.
[15] DEL-PORTO F,DI-GIOIA C,TRITAPEPE L,et al.The multitasking role of macrophages in stanford type A acute aortic dissection[J].Cardiology,2014,127(2):123-129.
[16] YUN S P,LEE S J,OH S Y,et al.Reactive oxygen species induce MMP12-dependent degradation of collagen 5 and fibronectin to promote the motility of human umbilical cord-derived mesenchymal stem cells[J].Br J Pharmacol,2014,171(13):3283-3297.
[17] GUO Z Y,JIANG L P.Matrix metalloproteinase 12(MMP12)as an adverse prognostic biomarker of vascular invasion in hepatic cell carcinoma[J].Eur Rev Med Pharmacol Sci,2022,26(7):2238-2249.
[18] LV F Z,WANG J L,WU Y,et al.Knockdown of MMP12 inhibits the growth and invasion of lung adenocarcinoma cells[J].Int J Immunopathol Pharmacol,2015,28(1):77-84.
[19] CHUNG I C,CHEN L C,CHUNG A K,et al.Matrix metalloproteinase 12 is induced by heterogeneous nuclear ribonucleoprotein K and promotes migration and invasion in nasopharyngeal carcinoma[J].BMC Cancer,2014,14:348.
[20] LUO Y H,YUAN L,LU D D,et al.The mechanism of dehydroandrographolide inhibiting metastasis in gastric cancer based on network pharmacology and bioinformatics[J].Medicine(Baltimore),2023,102(34):e34722.
[21] ZHANG W,LI G S,GAN X Y,et al.MMP12 serves as an immune cell-related marker of disease status and prognosis in lung squamous cell carcinoma[J].Peer J,2023,11:e15598.
[22] BERES B,YUSENKO M,PETERFI L,et al.Matrix metalloproteinase 12 is an independent prognostic factor predicting postoperative relapse of conventional renal cell carcinoma,a short report[J].Cell Oncol(Dordr),2022,45(1):193-198.
[23] GAO H,ZHOU X,LI H,et al.Role of matrix metallopeptidase 12 in the development of hepatocellular carcinoma[J].J Invest Surg,2021,34(4):366-372.
[24] XIE J,ZHOU X,WANG R,et al.Identification of potential diagnostic biomarkers in MMPs for pancreatic carcinoma[J].Medicine(Baltimore),2021,100(23):e26135.
[25] 刘爱东,刘时飞,熊光宜,等.真核翻译起始因子2α促进结直肠腺癌细胞增殖[J].中华实验外科杂志,2022,39(9):1752-1754.
[26] HE M K,LE Y,ZHANG Y F,et al.Matrix metalloproteinase 12 expression is associated with tumor FOXP3+ regulatory T cell infiltration and poor prognosis in hepatocellular carcinoma[J].Oncol Lett,2018,16(1):475-482.
[27] HAN F,ZHANG S,ZHANG L,et al.The overexpression and predictive significance of MMP-12 in esophageal squamous cell carcinoma[J].Pathol Res Pract,2017,213(12):1519-1522.

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备注/Memo

备注/Memo:
基金项目:辽宁省科学技术计划项目(2021-BS-268)
更新日期/Last Update: 2024-06-05