Differential Effects Of Low-dose Radiation On Nrf2Expression In Human Lung Epithelial Cells And Lung Cancer Cells

Lung cancer is one of the most common malignant tumors worldwide. In our country,incidence and mortality of lung cancer are situated the first place of malignant tumors incities, the incidence and mortality are increasing in the recent years, and more and moreresearchers are attracted by these situations.The conventional treatments for lung cancer include surgery, chemotherapy,radiotherapy, biological therapy, molecular targeted therapy and Traditional Chinesemedicine and so on. According to clinical statistics, only20%of patients with non-small celllung cancer have chance to accept radical surgery at the time of diagnosis. The5-yearsurvival rate of the cases after surgery is from30%to40%. Postoperative radiotherapy canimprove local control and survival rate of patients with lung cancer to a certain extent, and isused widely in clinical treatment. However, the radiotherapy will unavoidably cause damagein the normal tissues meanwhile killing cancer cells, that has become a major obstacle ofincreasing radiation dose for improving radiation efficacy. The decreased in the damage tonormal tissues when radiation treatment of tumors is an ideal result for tumor researchers.Low-dose radiation has hormesis and adaptive response in the normal cells. Low-doseradiation in combined with high-dose radiation in the clinic may cause synergistic killing effectson tumor cells, that have an important significance for the enhancement of radiotherapyefficacy and alleviation of the side effects of radiotherapy.In the recent years, the studies on the nuclear factor E2-related factor2(Nrf2) havebecome hot spots in the field of oxidative damage. Nrf2has been proved to be a key factor inadjustment of expression of many intracellular antioxidants. Nrf2possesses multiplebiological activities, such as keeping the oxidation-antioxidation balance in cells, inhibitingapoptosis, anti-inflammatory effect.In this study, the differential biological effects induced by low-dose radiation in humanepithelial cells and lung cancer cells has been studied, the changes of gene expressioninvolved to oxidative stress were detected, as well as the mechanisms were explored.In this study, the proliferation of normal lung epithelial cells(HBE) and lung cancercells(A549) at3,6,12,24and48h after low-dose radiation was detected by MTT assay; the proportion of cells in cell cycle stages was evaluated using flow cytometry, and the changesin the cell cycle in HBE cells and A549cells after low-dose radiation ware studied; Westernblot was used to detect expression of Nrf2in two kinds of cells at6h and24h after radiation;glutathione concentrations regulated by Nrf2in two kinds of cells were determined byELISA.Main results of the present study:(1) Proliferation of normal lung epithelial cells was noticeably accelerated after LDR,the proportion of S-phase cells was significantly increased; while the proliferation of lungcancer cells and the proportion of S-phase cells had no significant change, indicating thatLDR was able to induce hormesis, but LDR failed to induce hormesis in lung cancer cells.(2) Expression levels of Nrf2in normal lung epithelial cells were significantly increasedafter LDR, while expression levels of Nrf2in lung cancer cells did not markedly change.(3) After LDR, the glutathione concentrations of normal lung epithelial cells weresignificantly increased, while changes in glutathione concentrations in lung cancer cells werenot found.These results suggested that low-dose radiation induced differential oxidative stressresponse in normal lung epithelial cells and in lung cancer cells, and that may be one of themechanisms of low-dose radiation resulted in the differential biological effects in two kindsof cells.