Objective: To investigate the sensitivity to Adriamycin of down-regulated cells expressed hOGG1 gene which target to oxidative DNA damage and repair, and provide more experimental evidence of sensitizing the response of tumor to chemotherapy.
Methods: Human lung adenocarcinoma A549 cells and A549-R cells transfected with a ribozyme gene which inhibited the hOGG1 mRNA expression were studied. The viability of cells treated with Adriamycin at different dosage was detected by MTT test. Micronucleus rate, DNA damage and repair were detected by micronucleus test in vitro and single cell gel electrophoresis assay (SCGE); Apoptotic cell population, cell cycle distribution and cell proliferation index of the two kind of cells were determined by flow cytometry.
Results: The cell viability after treatment with Adriamycin was significantly lower in A549-R cells than in A549 cells (P<0.05). The micronucleus rate in A549-R cells was higher than A549 cells statistically (P < 0. 05). DNA damage of A549-R cells induced by Adriamycin at different dosage was more serious than A549 cells both in comet cell rate and DNA migration length. The DNA repair after treatment of Adriamycin happened late in both kinds of cells but had a big difference in the repair capability of the two kinds of cells. The repair capability in A549-R cells was significantly lower than that of A549 cells. The percentages of A549-R cells in G0/G1 phase were increased after treatment with Adriamycin. Additionally, the apoptosis percentages of cells were significantly increased in the two kinds of cells, and the cell proliferation index was decreased with the increase of Adriamycin dosage. These changes in A549-R cells were demonstrated more obviously than that of A549 cells.
Conclusion: Down-regulating of the expression of hOGG1 can decrease the DNA repair capability of A549 cells, and increase the sensitivity of cells to Adriamycin.