High concentrations of recombinant adenovirus expressing p16 gene induces apoptosis in lung cancer cell lines.
In this study, we discussed the effects of treatment with recombinant adenovirus expressing p16 (AX-p16) on cell growth and cell death. Ax-p16 at 10 m.o.i. groups showed growth inhibition 3 days after gene transfection, but the cells regrew and did not undergo cell death. On the other hand, Ax-p16 at 300 m.o.i. groups showed complete cell growth inhibition leading to cell death which was apparent 7 days after p16 gene transfection. In the high m.o.i. Ax-mock groups, cell death was marked just after infection, but had diminished by 7 days after infection. Downregulation of pRB was detected only in Ax-p16 at 300 m.o.i. groups. These data suggest that a) high m.o.i. condition of Ax-p16 gives therapeutic benefits due to the combined effects of adenovirus and high expression of p16; and b) the cell killing mechanism of the p16 transgene is different from that of high m.o.i. adenoviral infection.
Naruse
I
I
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
Heike
Y
Y
Hama
S
S
Mori
M
M
Saijo
N
N
D000260:Adenoviruses, Human; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D008175:Lung Neoplasms; D011994:Recombinant Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D016160:Retinoblastoma Protein / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D019941:Cyclin-Dependent Kinase Inhibitor p16; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein