+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Cooperative inhibition of renal cancer growth by anti-epidermal growth factor receptor antibody and protein kinase A antisense oligonucleotide



Cooperative inhibition of renal cancer growth by anti-epidermal growth factor receptor antibody and protein kinase A antisense oligonucleotide



Journal of the National Cancer Institute 90(14): 1087-1094



Background: The expression of epidermal growth factor receptor (EGFR) and type I cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKAI) is associated with neoplastic transformation. By use of human renal cancer cell lines (i.e., 769-P, ACHN, A498, and SW839), we investigated the antiproliferative activity and the antitumor activity of an anti-EGFR humanized chimeric mouse monoclonal antibody, MAb C225, and a novel mixed backbone 18-mer antisense oligonucleotide, HYB 190, that targets expression of the RIalpha regulatory subunit of PKAI. Methods: The antiproliferative activity of MAb C225 and oligonucleotide HYB 190, alone or in combination, on different renal cancer cell lines was determined by monitoring cell growth in soft agar. In addition, the induction of apoptosis by treatment with the anti-EGFR antibody and/or antisense PKAI oligonucleotides was evaluated by flow cytometric analysis of fragmented DNA. The antitumor activity of MAb C225 and oligonucleotide HYB 190 was determined in athymic mice bearing established ACHN tumor xenografts. Cell proliferation and tumor growth data were evaluated for statistical significance using Student's t test; reported P values are two-sided. Results: MAb C225 and oligonucleotide HYB 190 inhibited colony formation in soft agar in a dose-dependent manner for all renal cancer cell lines tested. We observed a potentiation of growth inhibition and induction of apoptosis when 769-P cells and ACHN cells were treated with both agents. Combination treatment with MAb C225 and oligonucleotide HYB 190 caused regression of ACHN tumor xenografts, whereas single-agent treatment only delayed tumor growth. Conclusion: The combination of anti-EGFR MAb C225 and HYB 190 antisense PKAI oligonucleotides HYB 190 exhibited cooperative antiproliferative effects and cooperative antitumor effects on EGFR and PKAI-expressing human renal cancer cell lines.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 008388618

Download citation: RISBibTeXText

PMID: 9672257

DOI: 10.1093/jnci/90.14.1087


Related references

Cooperative inhibition of human renal cancer cell growth by treatment with anti-epidermal growth factor receptor monoclonal antibody and a mixed backbone antisense oligonucleotide targeting type I protein kinase A. Proceedings of the American Association for Cancer Research Annual Meeting 39: 65, 1998

Cooperative inhibitory effect of novel mixed backbone oligonucleotide targeting protein kinase A in combination with docetaxel and anti-epidermal growth factor-receptor antibody on human breast cancer cell growth. Clinical Cancer Research 5(4): 875-881, 1999

Antitumor activity of combined treatment of human cancer cells with ionizing radiation and anti-epidermal growth factor receptor monoclonal antibody C225 plus type I protein kinase A antisense oligonucleotide. Clinical Cancer Research 6(11): 4343-4350, 2000

Synergistic antiproliferative effects of ionizing radiations with anti-epidermal growth factor receptor monoclonal antibody C225 and protein kinase A antisense oligonucleotide HYB 165. International Journal of Radiation Oncology Biology Physics 45(3 Suppl. ): 161, 1999

Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells. Clinical Cancer Research 6(9): 3739-3747, 2000

Oral administration of a novel taxane, an antisense oligonucleotide targeting protein kinase A, and the epidermal growth factor receptor inhibitor Iressa causes cooperative antitumor and antiangiogenic activity. Clinical Cancer Research 7(12): 4156-4163, 2001

A selective cyclooxygenase-2 inhibitor combined with the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 and protein kinase A antisense causes cooperative tumor growth inhibition after oral administration. Proceedings of the American Association for Cancer Research Annual Meeting 43: 1002, 2002

Effective inhibition of the epidermal growth factor/epidermal growth factor receptor binding by anti-epidermal growth factor antibodies is related to better survival in advanced non-small-cell lung cancer patients treated with the epidermal growth factor cancer vaccine. Clinical Cancer Research 14(3): 840-846, 2008

Inhibition of growth and induction of enzyme activities in a clonal human hepatoma cell line (Li-7A): comparison of the effects of epidermal growth factor and an anti-epidermal growth factor receptor antibody. Journal of Cellular Physiology 134(1): 109-116, 1988

Oral mixed-backbone oligonucleotide targeting protein kinase A causes inhibition of growth, angiogenesis and growth factor production and cooperative antitumor activity with cytotoxic drugs in human cancer xenografts. Proceedings of the American Association for Cancer Research Annual Meeting 40: 483, 1999

Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity. Journal of Biological Chemistry 259(12): 7755-7760, 1984

Combination of a selective cyclooxygenase-2 inhibitor with epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 and protein kinase A antisense causes cooperative antitumor and antiangiogenic effect. Clinical Cancer Research 9(4): 1566-1572, 2003

Cooperative antiproliferative effects of 8-Cl-cAMP and 528 anti-epidermal growth factor receptor monoclonal antibody on human cancer cells. Proceedings of the American Association for Cancer Research Annual Meeting 36: 436, 1995

Epidermal growth factor receptor blockage by fab2 fragments of anti epidermal growth factor receptor antibody 225 is as effective as complete antibody in inhibiting a431 xenograft growth. Proceedings of the American Association for Cancer Research Annual Meeting 33: 392, 1992

Antibody mediated receptor dimerization and downregulation enhance inhibition of A431 cell growth by anti-epidermal growth factor receptor monoclonal antibody. Clinical Research 42(2): 206A, 1994