IL-17-JAK2/STAT3 signaling pathway reduces chemo-induced apoptosis in hepatocellular carcinoma through regulating p53

Guo Bin; Guo Jiapei; Li Leilei; Wu Jinghua

doi:10.13406/j.cnki.cyxb.001166

您当前的位置：

首页 >

文章列表页 >

IL-17-JAK2/STAT3 signaling pathway reduces chemo-induced apoptosis in hepatocellular carcinoma through regulating p53

更新时间：2024-01-17

- IL-17-JAK2/STAT3 signaling pathway reduces chemo-induced apoptosis in hepatocellular carcinoma through regulating p53
- Journal of Chongqing Medical University Vol. 42, Issue 7, Pages: 845-849(2017)
- 作者机构：
  
  华北理工大学附属医院检验科
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.001166
  CLC： R735.7
- Published：2017，
扫描看全文
Guo Bin, Guo Jiapei, Li Leilei, et al. IL-17-JAK2/STAT3 signaling pathway reduces chemo-induced apoptosis in hepatocellular carcinoma through regulating p53. [J]. Journal of Chongqing Medical University 42(7):845-849(2017)
DOI：

Guo Bin, Guo Jiapei, Li Leilei, et al. IL-17-JAK2/STAT3 signaling pathway reduces chemo-induced apoptosis in hepatocellular carcinoma through regulating p53. [J]. Journal of Chongqing Medical University 42(7):845-849(2017) DOI： 10.13406/j.cnki.cyxb.001166.

摘要

目的:通过研究肝癌细胞激活白介素-17-蛋白酪氨酸激酶2/信号转导及转录激活因子3(IL-17-janus protein tyrosine kinase 2/signal transducers and activators 3 of transcription

IL-17-JAK2/STAT3)信号通路调控p53表达并下调化疗的凋亡敏感性

以此探讨肝癌细胞化疗耐药的机制。方法:选取我院2012年5月至2015年1月收治的肝癌患者(病理学确诊)及健康体检者各30例

ELISA检测肝癌患者化疗前后及正常对照组血清中白介素-17(interlrukin-17

IL-17)浓度;培养肝癌HepG2细胞

分别加入anti-IL-17R及IL-17后与奥沙利铂共培养

24 h后提取细胞蛋白

Western blot检测肝癌细胞凋亡相关蛋白BAX

Bcl-2表达情况及JAK2/STAT3信号通路活化情况及p53的表达情况;AG490特异性阻断JAK2/STAT3信号通路后检测p53的表达情况。结果:经奥沙利铂化疗后肝癌患者血清中IL-17的浓度[(143.96±33.20)pg/m L]明显高于化疗前[(77.36±15.66)pg/m L]及正常对照组[(26.61±4.95)pg/m L](P<0.05);肝癌细胞加入anti-IL-17R与奥沙利铂共培养24 h后

BAX表达量明显升高、Bcl-2表达量降低

磷酸化蛋白酪氨酸激酶(p-JAK2)、磷酸化信号转导及转录激活因子(p-STAT3)表达量均明显降低

p53表达量升高;而加入IL-17的肝癌细胞

BAX表达量明显降低、Bcl-2表达量明显升高

p-JAK2、p-STAT3表达量均明显升高

p53表达量明显降低。AG490阻断JAK/STAT通路后

肝癌细胞p53的表达水平明显升高。结论:肝癌细胞化疗过程中通过IL-17激活JAK2/STAT3信号通路调控p53的表达进而下调肝癌细胞凋亡敏感性

由此导致肝癌的化疗抵抗。

Abstract

Objective:To investigate the regulation of p53 expression by IL-17-janus protein tyrosine kinase 2/signal transducers and activators 3 of transcription（IL-17-JAK2/STAT3）signaling pathway and down-regulation of the apoptotic sensitivity to chemotherapy and to explore the mechanism of drug resistance in hepatocellular carcinoma（HCC）. Methods:Thirty cases of HCC（pathological diagnosis）and 30 cases of healthy physical examination in our hospital from May 2012 to January 2015 were chosen as research subjects.IL-17 level in serum was detected by ELISA. HepG2 cells were cultured and added to anti-IL-17 R

IL-17 and oxaliplatin co-culture for 24 hours

then the protein was exacted to detect the apoptosis related protein BAX and Bcl-2 and key nodes protein of JAK2/STAT3 signal pathway and the expression of p53 by Western blot. The expression of p53 was detected while JAK2/STAT3 pathway was blocked with AG490. Results:After chemotherapy

HCC patients serum IL-17 level [（143.96±33.20）pg/m L] was much higher than that before chemotherapy[（77.36±15.66）pg/m L] and that of healthy check-up group[（26.61±4.95）pg/m L]（P<0.05）. After HepG2 cells being cultured with anti-IL-17 R and oxaliplatin for 24 hours

the expression of BAX was increased while Bcl-2 was decreased

the expressions of p-jak2

p-STAT3 were significantly decreased while p53 was increased. After adding IL-17 to HepG2 cells

BAX was decreased while Bcl-2 was increased significantly

p-jak2

p-STAT3 were significantly increased while p53 was significantly reduced. After adding AG490 blocking agents

p53 expression was increased. Conclusion:IL-17 could regulate p53 expression through activated JAK2/STAT3 signaling pathway

which can reduce the chemotherapy sensitivity of HCC.

关键词

肝癌IL-17JAK2/STAT3信号通路p53化疗抵抗

Keywords

hepatocellular carcinomaIL-17JAK2/STAT3 signal pathwayp53chemotherapy-resistant

references

Views

448

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Promotion of the proliferation of hepatocellular carcinoma cells by acetyl-CoA carboxylase 2 through cell cycle regulation

Quantification of intrahepatic cccDNA,DNA,serum HBV DNA and its relationship with HBeAg in hepatitis B virus-related hepatocellular carcinoma

Inhibitory effects of AG490 on transplanted tumor of nude mice with live cancer through JAK2/STAT3 signal pathway and its mechanism

Association between intrahepatic levels and mutation of hepatitis B virus covalently closed circular DNA in hepatitis B virus-related hepatocellular carcinoma

Construction of GSTZ1 recombinant adenovirus and its effect on migration of hepatocarcinoma cells

Related Author

Zhang Zhirong

Wang Kai

Tang Ni

Huang Yao

Luo Xuan

Chen Yanmeng

Huang Ailong

Hu Yuan

Related Institution

Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education， Chongqing Medical University

Key Laboratory of Molecular Biology on Infectious Disease,Ministry of Education,Chongqing Medical University

Department of Clinical Nutrition,the First Affiliated Hospital of Hebei Medical University

Department of Medical Service,the First Affiliated Hospital of Hebei Medical University

Department of Cardiac Surgery,the First Affiliated Hospital of Hebei Medical University

⁰