Effects of adenovirus-mediated human cyclooxygenase-2 antisense RNA on the growth of hepatocellular carcinoma

World J Gastroenterol. 2005 Oct 21;11(39):6110-4. doi: 10.3748/wjg.v11.i39.6110.

Abstract

Aim: To investigate the relation between the expression of cyclooxygenase-2 (COX-2) and liver cancer, to construct the recombinant adenovirus encoding human COX-2 antisense RNA, and to explore its effects on liver cancer cell proliferation.

Methods: We studied the expression of COX-2 in 34 cases of hepatocellular carcinoma (HCC) and SMMC7402 and SMMC7721 by immunohistochemical technique. Recombinant adenovirus Ad-AShcox-2 was constructed and transfected into human HCC cell lines SMMC7402 and SMMC7721, and its effects on COX-2 expression, cell apoptosis and cell cycle were analyzed by flow cytometry. Cell proliferation was determined by colony-forming efficiency.

Results: We observed COX-2 expression in 82.4% of the HCC and SMMC7402 cells, but no COX-2 expression in SMMC7721 cells. In addition, recombinant adenovirus encoding antisense COX-2 fragment Ad-AShcox-2 was obtained with the titer of 1.06 x 10(12) PFU/mL. Ad-AShcox-2 could reduce the expression of COX-2 and enhance the percentage of cells in G(1)/G(0) phase in SMMC7402 cell line. The difference of apoptotic index between the Ad-AShcox-2 group and control group was statistically significant (t( control group ) = 32.62 and t( Ad-LacZ ) = 10.93, P<0.001) in SMMC7402 but not in SMMC7721. Similarly, colony-forming rates of SMMC7402 and SMMC7721 cell lines, after the transfer of Ad-AShcox-2, were (2.7+/-0.94)% and (33.6+/-4.24)%, respectively.

Conclusion: Reduction in the expression of COX-2 can inhibit COX-2 expressing HCC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Division
  • Cell Line, Tumor
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / metabolism
  • Genetic Therapy / methods*
  • Humans
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / therapy*
  • RNA, Antisense / pharmacology

Substances

  • RNA, Antisense
  • Cyclooxygenase 2