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HBx通过Notch信号通路在正常免疫小鼠体内导致肝癌的作用机制
Mechanism of hepatitis B virus X inducing hepatocellular carcinoma through Notch signaling pathway in a normal immune mouse model
- 第三军医大学学报 2021年43卷第10期 页码：883-891
- 作者机构：
- 作者简介：
- 基金信息：国家自然科学基金面上项目(81071770)
DOI：10.16016/j.1000-5404.202011152
中图分类号：收稿：2020-11-17，
纸质出版：2021-05-30
- 稿件说明：
移动端阅览
周梦瑶, 杜彬, 毋楠, 等. HBx通过Notch信号通路在正常免疫小鼠体内导致肝癌的作用机制[J]. 第三军医大学学报, 2021,43(10):883-891.
Mengyao ZHOU, Bin DU, Nan WU, et al. Mechanism of hepatitis B virus X inducing hepatocellular carcinoma through Notch signaling pathway in a normal immune mouse model[J]. Journal of Third Military Medical University, 2021, 43(10): 883-891.
周梦瑶, 杜彬, 毋楠, 等. HBx通过Notch信号通路在正常免疫小鼠体内导致肝癌的作用机制[J]. 第三军医大学学报, 2021,43(10):883-891. DOI： 10.16016/j.1000-5404.202011152.
Mengyao ZHOU, Bin DU, Nan WU, et al. Mechanism of hepatitis B virus X inducing hepatocellular carcinoma through Notch signaling pathway in a normal immune mouse model[J]. Journal of Third Military Medical University, 2021, 43(10): 883-891. DOI： 10.16016/j.1000-5404.202011152.
摘要
Abstract
Objective
2
To construct a normal immune mouse model carrying hepatitis B virus X (HBx) for long term so as to explore the possible mechanism of HBx causing hepatocellular carcinoma (HCC).
Methods
2
Hepatic progenitor cells transfected with HBx were injected into Kunming mice
via
hepatic portal vein to construct the animal model. The liver tissues were harvested at 30
90
180 and 360 d after injection
respectively. The expression of HBx as well as that of Notch1
Notch4 and Hes1 at protein and mRNA levels was detected by Western blotting and RT-qPCR
respectively
and the histopathological changes were observed by HE staining. In addition
a novel γ-secretase inhibitor
DAPT
was intraperitoneally injected at 180 d
and then Western blotting and RT-qPCR were adopted to determine the changes in the expression of apoptosis and cell-cycle-related factors.
Results
2
The animal model was successfully constructed
and liver cancer occurred at 360 d. Compared with the control group
the mRNA and protein levels of Notch1
Notch4 and Hes1 were all significantly increased in the HBx group at 30 d (
P
<
0.05
P
<
0.05
P
<
0.001)
and continued to 360 d (
P
<
0.05
P
<
0.05
P
<
0.01); the protein and mRNA levels of Bcl-2
CDK4
CyclinE and CyclinD1 were also up-regulated (protein:
P
<
0.001
P
<
0.01
P
<
0.001
P
<
0.01; mRNA:
P
<
0.05
P
<
0.001
P
<
0.001
P
<
0.01)
while those of Bax down-regulated in the HBx group (
P
<
0.001;
P
<
0.001). However
the inhibitor DAPT significantly reversed the above trends.
Conclusion
2
HBx causes anti-apoptosis and abnormal cell cycle changes in mice through persistent activation of the Notch pathway
and then ultimately leads to HCC.
关键词
Keywords
references
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