Study Of Inhibition Of Heme Oxygenase-1 On The Radiosensitivity In Lung Cancer A549 Cells

Background:In recent years, cancer has become one of these diseases threatening human health. More than 6 million people die from cancer every year worldwide, and more than 1 million people have been killed by lung cancer. Now, lung cancer has become the main cancer in developed countries. The mortality of lung cancer comes in third place only behind gastric cancer and liver cancer in China. However, Non-small cell lung cancer (NSCLC) accounts for more than 85% of all types of lung cancer. The effect of radiotherapy for NSCLC has been unsatisfactory. The main reason is the lower sensitivity of radiotherapy in cancer cells, especially in hypoxic tumor cells which is resistant to radiation. So the hotspot in Radiation Oncology focuses on how to enhance the radiosensitivity of lung adenocarcinoma. Recent studies have found that heme oxygenase-1 (HO-1) is highly expressed in many tumors such as melanoma, liver cancer, renal cell carcinoma, prostate cancer, lung cancer, pancreatic cancer and so on. Overexpression of HO-1 can promote tumor growth, inhibit apoptosis of tumor cell, induce angiogenesis, and reduce the chemosensitivity. However, little issue reported whether overexpression of HO-1 in cancer can reduce sensitivity to radiotherapy or not. And no issue report whether inhibition of HO-1 can enhance the radiosensitivity in human lung adenocarcinoma A549 Cells or not.Objective:To study that whether radiotherapy can change the expression of HO-1 in human lung adenocarcinoma A549 Cells and how to influence radiotherapy effect when the expression of HO-1 changes.Methods:Zinc protoporphyrinⅪ(Znpp) is inhibitor of HO-1. Human lung adenocarcinoma A549 Cells was the experimental subject. A549 Cells was randomly divided into four groups:control group, Znpp group, irradiation group(IR group), and Znpp+IR group. The control group was treated with nothing. Znpp group was treated with 12μmol/L Znpp for 24 hours and then detected by assays. IR group was treated by 2Gy,4Gy,8Gy dose of X-ray radiation and then detected by assays after 24 hours. Znpp+IR group was firstly treated by 12 u mol/L Znpp for 24 hours and secondly exposed to 2Gy,4Gy,8Gy dose of X-ray radiation and then detected by assays after 24 hours. The assays included relative expression of HO-1 mRNA, cell viability percentage, colony-forming fraction, apoptosis rate, and cell cycle distribution, and so on.Results:Relative expression of HO-1 mRNA in Znpp group was less than that in control group. Relative expression of HO-1 mRNA in IR group was obviously more than that in control group. And with the increasing doses of irradiation, relative expression of HO-1 mRNA in IR group enhanced. Compared to IR group, relative expression of HO-1 mRNA in Znpp+IR group reduced and was still higher than that in control group. Meanwhile, compared to control group, the cell viability percentage and colony-forming fraction in Znpp group reduced. There was statistical significance between the two group mentioned above (P<0.05). There was no difference of apoptosis rate between the two groups (P>0.05). The rate of G1 phase in Znpp group was highest in all groups. Compared to IR group, cell viability percentage and colony-forming fraction in Znpp+IR group reduced and apoptosis rate increased. There was statistically significance between IR group and Znpp+IR group (P<0.05).Conclusions:Irradiation can increase expression of HO-1 in human lung adenocarcinoma A549 Cells. Znpp can inhibit expression of HO-1 in A549 Cells. Low expression of HO-1 obviously increased lethal effect of irradiation and apoptosis rate of cells. Finally, inhibition of HO-1 can enhance the radiosensitivity in A549 Cells.