An agent that increases tumor suppressor transgene product coupled with systemic transgene delivery inhibits growth of metastatic lung cancer in vivo.
Low levels of gene expression following systemic delivery have impaired the effectiveness of tumor suppressor gene replacement in treating metastases. We asked whether combined treatment with 2-methoxyestradiol (2-Me), which increases levels of wild-type p53 protein in cancer cells, and the systemic administration of an adenoviral vector expressing wild-type p53 (Ad-p53) would inhibit the growth of human metastatic lung cancer cells in vivo. The simultaneous administration of p53 and 2-Me resulted in a greater than additive reduction with the lung colony count reduced to 33% of its control value. These results suggest that the synergistic effect of 2-Me and Ad-p53 in combination treatment may have application in the systemic treatment of cancer.
Kataoka
M
M
Department of Thoracic and Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Schumacher
G
G
Cristiano
R J
RJ
Atkinson
E N
EN
Roth
J A
JA
Mukhopadhyay
T
T
D000077584:2-Methoxyestradiol; D000256:Adenoviridae / Q000235:genetics; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016158:Genes, p53; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D016159:Tumor Suppressor Protein p53; D004958:Estradiol; D000077584:2-Methoxyestradiol