[Ectogenous fragile histidine triad gene inhibits the malignant phenotype of human lung cancer cell line A549 in vitro and in vivo].
OBJECTIVE
To investigate the inhibition effects of fragile histidine triad (FHIT) gene on the malignant growth of A549 cell line.


METHODS
A mammalian expression vector PEGFP-FHIT was constructed and transfected into the A549 cell line by lipofectamine. Then the transfected cell line was screened by G418. Individual G418-resistant colonies were isolated by limited dilution. The monoclonal transfected cell line was screened by RT-PCR and immunochemical staining. The inhibition growth efficacy of extraneous FHIT was evaluated by clonogenic survival assay, flow cytometry and heteroplastic transplant on nude mice.


RESULTS
Presence of extraneous FHIT gene in FHIT-A549 cell was proved by RT-PCR. Immunochemical stain demonstrated that the expression of extraneous FHIT protein was positive in FHIT-A549 cell and negative in PEGFP-A549 cell and A549 cell. The clonal formation rate of FHIT-A549 (2.6%) was significantly lower than that of A549 cell (50.1%) and PEGFP-A549 cell (53.6%, P < 0.01). FHIT-A549 cell (95.8%) was blocked in G(2) phage. Tumorigenicity of A549 cells in nude mice was greatly inhibited by expression of ectogenous FHIT gene. The weight of tumor was significantly lower in FHIT-A549 cell (0.04 +/- 0.03) than in A549 cell (0.24 +/- 0.11) and PEGFP-A549 cell (0.25 +/- 0.07, P < 0.01).


CONCLUSIONS
Reintroduction of the expression of ectogeneous FHIT gene can obviously suppress the proliferation and tumorigenicity in human lung cancer cell line A549 and induce apoptosis. The data demonstrate oncosuppressive properties of FHIT gene.
Zhang
Li-qun
LQ
Laboratory of Cellular and Biology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Wang
Hui
H
Lai
Bai-tang
BT
Yue
Wen-tao
WT
Zhan
Xiu-ping
XP
Yang
Xue-hui
XH
Zhang
Chun-yan
CY
Zhang
Tong-mei
TM
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D014162:Transfection; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase