[Effects of ectogenous FHIT gene on reversing malignant phenotype of human lung adenocarcinoma cells A549].

Objective: To explore the role of fragile histidine triad(FHIT) gene in the proliferation, apoptosis and tumorigenesis of human lung cancer cells.

Methods: FHIT gene packaged with lipofectin was transfected into the cells of a human lung adenocarcinoma cell line (A549), which stably expressed ectogenous FHIT gene. The FHIT mRNA and protein expression of A549-FHIT, A549-vector and A549 cell were detected by reverse transcription-PCR(RT-PCR), Western blot and immunocytochemical methods. The cell cycle pattern and apoptosis were assayed by using flow cytometry.

Results: After transfection of FHIT gene, cell growth was obviously inhibited (P<0.01). The apoptosis index of A549-FHIT (8.42%) was significantly higher than that of A549-vector (5.45%) and A549 cells (5.71%)(P<0.01). The clone-formation rate of A549-FHIT cell (21.84%) was significantly lower than that of A549-vector (28.70%) and A549 cells (31.68%, P<0.01). Compared with control cell lines, larger scale of A549-FHIT cells accumulated in G0/G1, presenting that the proportion of the cells in G0/G1 phase was obviously increased from 67.78 % to 82.35 %. Tumorigenicity of the A549 cells in nude mice was greatly inhibited by expression of ectogenous FHIT gene, the weight and volume of A549-FHIT(1.61 g/1.37 cm(3)) were significantly lower than that of A549-vector (2.45 g/1.99cm(3)) and A549 cells (2.77 g/2.27 cm(3))(P<0.05).

Conclusion: Expression of ectogenous FHIT gene can obviously inhibit the proliferation and tumorigenesis of A549 cells, and can induce A549 cells into programmed cell death. The result of this study suggests that FHIT gene may be a tumor suppressor gene in human lung cancer cells.