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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)

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 -