[1]王艳军,王高雄,黄天从,等.高迁移率族蛋白1通过调控Erk1/2、Cyclin D1及MMP14蛋白促进肝内胆管细胞癌进展[J].第三军医大学学报,2019,41(05):430-436.
 WANG Yanjun,WANG Gaoxiong,HUANG Tiancong,et al. HMGB1 promotes progression of intrahepatic cholangiocarcinoma through regulating Erk1/2, Cyclin D1 and MMP14 proteins[J].J Third Mil Med Univ,2019,41(05):430-436.
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高迁移率族蛋白1通过调控Erk1/2、Cyclin D1及MMP14蛋白促进肝内胆管细胞癌进展(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第05期
页码:
430-436
栏目:
基础医学
出版日期:
2019-03-15

文章信息/Info

Title:
 HMGB1 promotes progression of intrahepatic cholangiocarcinoma through regulating Erk1/2, Cyclin D1 and MMP14 proteins
作者:
福建医科大学附属第二医院肝胆外科
 
Author(s):
WANG Yanjun WANG Gaoxiong HUANG Tiancong LI Xinfeng

Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, China

关键词:
肝内胆管细胞癌高迁移率族蛋白1细胞外信号调控激酶细胞周期蛋白1基质金属蛋白酶14
Keywords:
intrahepatic cholangiocarcinoma high mobility group box1 extracellular signal regulated kinase cyclin D1 matrix metalloproteinases 14
分类号:
R341; R363.21; R735.8
文献标志码:
A
摘要:

目的 探讨高迁移率族蛋白1(high mobility group box1, HMGB1)在肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)进展中的作用及机制。方法 运用免疫组化法检测75例ICC癌组织石蜡标本中HMGB1蛋白表达情况,分析其表达水平与临床病理特征关系;在体外,外源性HMGB1处理细胞及siRNA抑制HMGB1表达后运用CCK8、细胞迁移、侵袭试验研究HMGB1对肝内胆管癌细胞恶性生物学行为的影响;运用westernblot检测细胞内蛋白。结果 免疫组化检测结果显示54.67%(41/75)的肝内胆管细胞癌组织过表达HMGB1蛋白,HMGB1过表达与肿瘤分化程度(P=0.019)、临床分期(P=0.017)及血管侵犯(P=0.033)有明显正相关性。CCK8结果显示HMGB1可以促进肝内胆管癌细胞HuCCT1的增殖(P<0.05)。细胞迁移试验显示外源性HMGB1处理后细胞迁移数目增加到空白组的(1.85±0.08)倍(P<0.01); 同时,siRNA抑制细胞HMGB1表达后细胞迁移数目减弱到空白组的(0.48±0.04)倍 (P<0.01)。同样地,细胞侵袭试验结果显示外源性HMGB1处理后的HuCCT1细胞穿过基质胶的数目增加到空白组的(1.46±0.05)倍(P<0.01);siRNA抑制细胞HMGB1表达后细胞侵袭数目减弱到空白组的(0.67±0.07)倍(P<0.01)。Western blot结果显示外源性HMGB1处理HuCCT1细胞后细胞内Erk1/2、Cyclin D1及MMP14蛋白表达明显增加;siRNA沉默HMGB1表达后细胞内MMP14蛋白表达减弱。结论 HMGB1在肝内胆管细胞癌的进展中发挥作用,其机制可能与调控Erk1/2、Cyclin D1及MMP14蛋白相关。 

Abstract:

Objective To explore the effect and the mechanism of high mobility group box1 (HMGB1) in the progression of intrahepatic cholangiocarcinoma (ICC). Methods The expression of HMGB1 in ICC specimens obtained from 75 patients was examined by immunohistochemistry (IHC). The correlation between HMGB1 expression level and clinicopathologic characteristics was analyzed. In in vitro study, ICC cells were treated with exogenous HMGB1 and siRNA, then the effect of HMGB1 on ICC cells malignant biological behavior was assessed using CCK8 assay, cell migration and invasion assay. Western blot analysis was used to detect intracellular proteins. Results IHC results showed that overexpression of HMGB1 was found in 54.6% (41/75) ICCs. The overexpression of HMGB1 was significantly correlated with tumor differentiation grade (P=0.019), TNM stage (P=0.017) and vessel invasion (P=0.033). CCK8 assay showed that exogenous HMGB1 promoted the proliferation of HuCCT1 cells (P<0.05). Cell migration assay indicated that exogenous HMGB1 treatment promoted cell migration by 1.85±0.28 fold (P<0.01), and siRNA treatment reduced cell migration by 0.48±0.04 fold (P<0.01). Similarly, exogenous HMGB1 increased invasion of HuCCT1 cells by 1.46±0.05 fold (P<0.01) through matrigel layer, and siRNA treatment reduced cell invasion by 0.67±0.07 (P<0.01). Western blotting indicated that the expression of Erk1/2, Cyclin D1 and MMP14 were upregulated in the cells treated with exogenous HMGB1. Moreover, Western blot results showed that suppression of HMGB1 by siRNA induced the downregulation of MMP14. Conclusion HMGB1 plays a role in the progression of ICC, and the mechanism may be involved in the regulation of Erk1/2, Cyclin D1 and MMP14 proteins

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更新日期/Last Update: 2019-03-05