Mechanism of hepatitis B virus X inducing hepatocellular carcinoma in mice through COX-2 and its downstream factors

Nan WU; Mengyao ZHOU; Bin DU; Xin HUANG; Siyao ZHANG; Qin KUANG; Yong WU; Tao FENG

doi:10.16016/j.1000-5404.202011103

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Mechanism of hepatitis B virus X inducing hepatocellular carcinoma in mice through COX-2 and its downstream factors

更新时间：2026-01-09

- Mechanism of hepatitis B virus X inducing hepatocellular carcinoma in mice through COX-2 and its downstream factors
- Journal of Third Military Medical University Vol. 43, Issue 10, Pages: 892-899(2021)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81071770)
- DOI：10.16016/j.1000-5404.202011103
  CLC：
- Received：11 November 2020，
  
  Published：30 May 2021
- 稿件说明：
移动端阅览
Nan WU, Mengyao ZHOU, Bin DU, et al. Mechanism of hepatitis B virus X inducing hepatocellular carcinoma in mice through COX-2 and its downstream factors[J]. Journal of Third Military Medical University, 2021, 43(10): 892-899.
DOI：

Nan WU, Mengyao ZHOU, Bin DU, et al. Mechanism of hepatitis B virus X inducing hepatocellular carcinoma in mice through COX-2 and its downstream factors[J]. Journal of Third Military Medical University, 2021, 43(10): 892-899. DOI： 10.16016/j.1000-5404.202011103.

摘要

Abstract

Objective

To investigate the dynamic changes and the roles of COX-2 and its downstream factors in the carcinogenic process using a mouse model stably expressing hepatitis B virus X (HBx).

Methods

The expression of HBx in HBx-EGFP-14-19 cells was detected by Western blotting and RT-qPCR. A mouse model with stable expression of HBx was then established by injecting HBx-EGFP-14-19 cells into KM mice

via

hepatic portal vein. The mice were subsequently sacrificed at 30

180 and 360 d

respectively

and the liver tissues were collected. Western blotting

RT-qPCR and immunohistochemical assay were used to detect the expression of HBx in the liver; HE staining was adopted to observe the pathological characteristics of liver tissues. In addition

Western blotting and RT-qPCR were also employed to determine the expression changes of COX-2 and its downstream factors

cell cycle- and apoptosis-related factors in the liver tissues

at both mRNA and protein levels.

Results

The animal model with long-term stable expression of HBx was successfully constructed and eventually developed into liver cancer. The mRNA and protein levels of COX-2 and its downstream factor VEGF were continuously up-regulated even in 90 d after HBx was transferred into mice and the increment was continued until tumorigenesis (

0.05). The protein and mRNA levels of liver pro-apoptotic factors Bad and Bax were decreased (

0.05)

while those of the anti-apoptotic factor Bcl-2 were increased (

0.05)

and the levels of cell cycle factors Cyclin D1 and CDK4 were increased (

0.05). However

the effects of HBx on the above genes were reversed after administration of COX-2 inhibitor celecoxib.

Conclusion

HBx can cause liver cancer

which may be related to the up-regulation of COX-2 and its downstream factors.

关键词

Keywords

references

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