TY - JOUR
T1 - Induction of apoptosis and inhibition of tumorigenicity and tumor growth by adenovirus vector-mediated fragile histidine triad (FHIT) gene overexpression
AU - Ji, Lin
AU - Fang, Bingliang
AU - Yen, Nancy
AU - Fong, Kwun
AU - Minna, John D.
AU - Roth, Jack A.
PY - 1999/7/15
Y1 - 1999/7/15
N2 - We studied the effects of fragile histidine triad (FHIT) gene overexpression mediated by an adenoviral vector, Ad-FHIT, on cell proliferation, apoptosis, and cell cycle kinetics in human cancer cells and on tumorigenicity and tumor growth in nude mice. Overexpression of the FHIT gene significantly inhibited cell growth in various Ad-FHIT-transduced human lung cancer cells and head and neck carcinoma cells with FHIT gene abnormalities, but not in normal human bronchial epithelial cells. Fewer than 20% of cells in all Ad-FHIT-transduced cells survived at 7 days after transduction. Overexpression of the FHIT gene induced cell apoptosis and altered cell cycle processes. The apoptotic cell population markedly increased, and cells accumulated in S phase after Ad-FHIT transduction. The tumorigenicity of human H1299 lung cancer cells transduced by Ad-FHIT, in comparison with that of the control transductants and untreated cells, was eliminated in vivo. Subcutaneous tumor growth in nude mice who received intratumoral injections of Ad-FHIT, at a total dose of 3 x 1010 plaque- forming units/tumor for H1299 tumors and 4 x 1010/tumor for A549 tumors, were suppressed by more than 85% and 90%, respectively, compared with that in nude mice who received injections of empty vector at the same dose or with PBS alone. Together, our results suggest that the FHIT gene, when delivered at high efficiency by a recombinant adenoviral vector, functions as a tumor suppressor gene both in vitro and in vivo.
AB - We studied the effects of fragile histidine triad (FHIT) gene overexpression mediated by an adenoviral vector, Ad-FHIT, on cell proliferation, apoptosis, and cell cycle kinetics in human cancer cells and on tumorigenicity and tumor growth in nude mice. Overexpression of the FHIT gene significantly inhibited cell growth in various Ad-FHIT-transduced human lung cancer cells and head and neck carcinoma cells with FHIT gene abnormalities, but not in normal human bronchial epithelial cells. Fewer than 20% of cells in all Ad-FHIT-transduced cells survived at 7 days after transduction. Overexpression of the FHIT gene induced cell apoptosis and altered cell cycle processes. The apoptotic cell population markedly increased, and cells accumulated in S phase after Ad-FHIT transduction. The tumorigenicity of human H1299 lung cancer cells transduced by Ad-FHIT, in comparison with that of the control transductants and untreated cells, was eliminated in vivo. Subcutaneous tumor growth in nude mice who received intratumoral injections of Ad-FHIT, at a total dose of 3 x 1010 plaque- forming units/tumor for H1299 tumors and 4 x 1010/tumor for A549 tumors, were suppressed by more than 85% and 90%, respectively, compared with that in nude mice who received injections of empty vector at the same dose or with PBS alone. Together, our results suggest that the FHIT gene, when delivered at high efficiency by a recombinant adenoviral vector, functions as a tumor suppressor gene both in vitro and in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0033565920&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033565920&partnerID=8YFLogxK
M3 - Article
C2 - 10416589
AN - SCOPUS:0033565920
SN - 0008-5472
VL - 59
SP - 3333
EP - 3339
JO - Cancer Research
JF - Cancer Research
IS - 14
ER -