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[The expression of hepatitis B virus X protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma: correlation with microangiogenesis and metastasis, and what is the possible mechanism].
Zhonghua Gan Zang Bing Za Zhi. 2010 Nov; 18(11):831-6.ZG

Abstract

OBJECTIVE

To investigate the expression of HBx and COX-2 in hepatitis B virus-related hepatocellular carcinoma, and Its correlation with microangiogenesis and metastasis, and possible mechanism.

METHODS

Immunohistochemistry was used to detect the expression of hepatitis B virus X, cyclooxygenase-2 and CD34 in hepatitis B virus related hepatic carcinoma and 22 non-HBV related hepatic carcinoma tissues. The expression of hepatitis B virus x protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma correlated with microangiogenesis and metastasis was tested by Spearman correlation analysis. The expression of COX-2 in HepG2-X was detected by Western blot and RT-PCR. PGE2 was detected by ELISA in clear supernatant liquid of HepG2-X. Trypan blue exclusion was performed to examine the inhibitory effects of COX-2 selective inhibitor (celecoxib).

RESULTS

In Hepatitis B carcinoma tissue, HBx and COX-2 were expressed at high level. The positive rate of COX-2 expression was 88.87% (55/62) in HBx positive expression group, which was significantly higher than that of the positive expression 31.82% (7/22, x2=27.188, P<0.01) in HBx negative expression group and 40.91% (9/22, x2=20.453, P<0.01) in non-HBV related hepatic carcinoma tissues, but it had no statistical difference (x2=0.393, P=0.531) between the HBx negative expression group and non-HBV related hepatic carcinoma tissue group. The expressions of HBx and COX-2 in metastasis group were higher than that in non-metastasis group (P<0.01), MVD in HBx or COX-2 positive expression group was significantly higher than that in negative expression group and non-HBV related hepatic carcinoma tissues (P is less than 0.01). MVD with metastasis was higher than that without metastasis (P<0.01) and MVD with portal vein invasion was higher than that without invasion (P<0.05). Spearman correlation analysis showed that the expression of COX-2 was significantly correlated with the expression of HBx (Rs=0.568, P<0.01). Celecoxib suppressed the growth of both cells in a dose-dependent manner. HepG2-X was significantly susceptible to celecoxib as compared to the HepG2-PC cells. COX-2 protein and mRNA were upregulated in HepG2-X cells than in HepG2-PC. Moreover, PGE2 was upregulated in clear supernatant liquid of HepG2-X than in HepG2-PC.

CONCLUSION

The expressions of HBx and COX-2 were higher in HBV-related hepatocellular carcinoma. COX-2 was significantly correlated with HBx in HCC and it could be a key factor involved in HBx contributed hepatocellular carcinoma's microangiogenesis and metastasis. The possible mechanism of the dual effects might be through HBx, COX-2 and PGE2 pathways in infiltration involved metastasis and microangiogenesis involved metastasis.

Authors+Show Affiliations

The Affiliated Hospital of Xi'an Medical College, Xi'an 710077, China. kaigeliu@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

21138631

Citation

Liu, Kai-ge, et al. "[The Expression of Hepatitis B Virus X Protein and Cyclooxygenase-2 in Hepatitis B Virus-related Hepatocellular Carcinoma: Correlation With Microangiogenesis and Metastasis, and what Is the Possible Mechanism]." Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, vol. 18, no. 11, 2010, pp. 831-6.
Liu KG, Shao XL, Xie HH, et al. [The expression of hepatitis B virus X protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma: correlation with microangiogenesis and metastasis, and what is the possible mechanism]. Zhonghua Gan Zang Bing Za Zhi. 2010;18(11):831-6.
Liu, K. G., Shao, X. L., Xie, H. H., Xu, L., Zhao, H., Guo, Z. H., Li, L., & Liu, J. (2010). [The expression of hepatitis B virus X protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma: correlation with microangiogenesis and metastasis, and what is the possible mechanism]. Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, 18(11), 831-6. https://doi.org/10.3760/cma.j.issn.1007-3418.2010.11.010
Liu KG, et al. [The Expression of Hepatitis B Virus X Protein and Cyclooxygenase-2 in Hepatitis B Virus-related Hepatocellular Carcinoma: Correlation With Microangiogenesis and Metastasis, and what Is the Possible Mechanism]. Zhonghua Gan Zang Bing Za Zhi. 2010;18(11):831-6. PubMed PMID: 21138631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [The expression of hepatitis B virus X protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma: correlation with microangiogenesis and metastasis, and what is the possible mechanism]. AU - Liu,Kai-ge, AU - Shao,Xiao-li, AU - Xie,Hua-hong, AU - Xu,Li, AU - Zhao,Hui, AU - Guo,Zhan-hong, AU - Li,Li, AU - Liu,Jie, PY - 2010/12/9/entrez PY - 2010/12/9/pubmed PY - 2011/12/16/medline SP - 831 EP - 6 JF - Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology JO - Zhonghua Gan Zang Bing Za Zhi VL - 18 IS - 11 N2 - OBJECTIVE: To investigate the expression of HBx and COX-2 in hepatitis B virus-related hepatocellular carcinoma, and Its correlation with microangiogenesis and metastasis, and possible mechanism. METHODS: Immunohistochemistry was used to detect the expression of hepatitis B virus X, cyclooxygenase-2 and CD34 in hepatitis B virus related hepatic carcinoma and 22 non-HBV related hepatic carcinoma tissues. The expression of hepatitis B virus x protein and cyclooxygenase-2 in hepatitis B virus-related hepatocellular carcinoma correlated with microangiogenesis and metastasis was tested by Spearman correlation analysis. The expression of COX-2 in HepG2-X was detected by Western blot and RT-PCR. PGE2 was detected by ELISA in clear supernatant liquid of HepG2-X. Trypan blue exclusion was performed to examine the inhibitory effects of COX-2 selective inhibitor (celecoxib). RESULTS: In Hepatitis B carcinoma tissue, HBx and COX-2 were expressed at high level. The positive rate of COX-2 expression was 88.87% (55/62) in HBx positive expression group, which was significantly higher than that of the positive expression 31.82% (7/22, x2=27.188, P<0.01) in HBx negative expression group and 40.91% (9/22, x2=20.453, P<0.01) in non-HBV related hepatic carcinoma tissues, but it had no statistical difference (x2=0.393, P=0.531) between the HBx negative expression group and non-HBV related hepatic carcinoma tissue group. The expressions of HBx and COX-2 in metastasis group were higher than that in non-metastasis group (P<0.01), MVD in HBx or COX-2 positive expression group was significantly higher than that in negative expression group and non-HBV related hepatic carcinoma tissues (P is less than 0.01). MVD with metastasis was higher than that without metastasis (P<0.01) and MVD with portal vein invasion was higher than that without invasion (P<0.05). Spearman correlation analysis showed that the expression of COX-2 was significantly correlated with the expression of HBx (Rs=0.568, P<0.01). Celecoxib suppressed the growth of both cells in a dose-dependent manner. HepG2-X was significantly susceptible to celecoxib as compared to the HepG2-PC cells. COX-2 protein and mRNA were upregulated in HepG2-X cells than in HepG2-PC. Moreover, PGE2 was upregulated in clear supernatant liquid of HepG2-X than in HepG2-PC. CONCLUSION: The expressions of HBx and COX-2 were higher in HBV-related hepatocellular carcinoma. COX-2 was significantly correlated with HBx in HCC and it could be a key factor involved in HBx contributed hepatocellular carcinoma's microangiogenesis and metastasis. The possible mechanism of the dual effects might be through HBx, COX-2 and PGE2 pathways in infiltration involved metastasis and microangiogenesis involved metastasis. SN - 1007-3418 UR - https://www.unboundmedicine.com/medline/citation/21138631/[The_expression_of_hepatitis_B_virus_X_protein_and_cyclooxygenase_2_in_hepatitis_B_virus_related_hepatocellular_carcinoma:_correlation_with_microangiogenesis_and_metastasis_and_what_is_the_possible_mechanism]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=1007-3418&amp;year=2010&amp;vol=18&amp;issue=11&amp;fpage=831 DB - PRIME DP - Unbound Medicine ER -