Growth inhibitory effect of anti-K-ras adenovirus on lung cancer cells.
An adenoviral vector carrying a 2-Kb fragment of the K-ras proto-oncogene inserted in antisense orientation with respect to the cytomegalovirus promoter was constructed and used to infect H460a lung cancer cells (codon 61 K-ras mutation). The gene was efficiently transferred, and a high level of expression of antisense K-ras was achieved. At a multiplicity of infection to achieve 65% transduction of cells, the expression of K-ras protein was reduced by 70% in the lung cancer cell line H460a as compared with cells infected with control vectors or noninfected cells. This reduction produced a 47% inhibition of monolayer growth and a 90% inhibition of colony formation. At a similar level of transduction in the cell line H358 (codon 12 K-ras mutation), a 59% inhibition of monolayer growth compared with control vectors occurred; however the inhibition of H322 cells (wild-type k-ras) growth was no different than control vector infected cells. These data suggest that the adenoviral K-ras H322a antisense vector may have therapeutic potential in tumors in which K-ras is mutated.
Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
R
R
Alemany
S
S
Ruan
M
M
Kataoka
P E
PE
Koch
T
T
Mukhopadhyay
R J
RJ
Cristiano
J A
JA
Roth
W W
WW
Zhang
D000256:Adenoviridae / Q000235:genetics*; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D016372:RNA, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016372:RNA, Antisense