The Regulation Of Hypoxia-Induced Expression Of HIF-1α And OPN MRNAs And The In Vitro Radiosentization By Tirapazamine In Human Nasopharygeal Carcinoma Cells

Background and Objective: To study the hypoxia-induced expression of HIF-1αand osteopontin (OPN) mRNAs in human nasopharygeal carcinoma HNE-1 and CNE-1 cells and the radiosensitization of tirapazamine(TPZ), a hypoxia-specific drug, on HNE-1 and CNE-1 cells in vitro.Methods: The IC50 values of TPZ for HNE-1 and CNE-1 cells were measured using MTT assay ,and the expression of HIF-1αand OPN mRNAs in HNE-1 and CNE-1 cells were determined by using RT-PCR technique under aerobic and hypoxia conditions, respectively. The survival fractions of HNE-1 and CNE-1 cells treated with or without TPZ at IC10 in the presence or absence of oxygen for 6 hr were determined using colony forming assay following exposure to 1～6 Gy dose of 60Co radiation,and then the dose-survival curves were plotted and the values of D0,Dq and SER were calculated as a single-hit multitarget model.Results: The IC50 values of TPZ for HNE-1 and CNE-1 cells under aerobic condition were 34.81μmol/L;35.02μmol/L;The IC50 values of TPZ for HNE-1 and CNE-1 under hypoxic condition were 30.20μmol/L,28.48μmol/L; The expression of HIF-1αand OPN mRNAs were reduced by TPZ in HNE-1 cells, not in CNE-1 cells under hypoxic condition; The values of D0 and Dq for HNE-1 and CNE-1 cells following irradiation under aerobic and hypoxic conditions were 0.89Gy, 0.28Gy and 0.72Gy, 0.68Gy, and 1.47Gy, 0.44Gy and 0.95Gy, 0.56Gy, respectively. The values of D0 and Dq for HNE-1 and CNE-1 cells treated with TPZ under hypoxic condition following irradiation were 0.66Gy, 0.21Gy and 0.85Gy, 0.79Gy, respectively.Conclusions: Our findings showed TPZ would down-regulated hypoxia-induced increased expression of HIF-1αand OPN mRNAs of HNE-1 cells and radiosensitize HNE-1 cells but not CNE-1 cells, and act as a hypoxia modifier.