Regulation of hypoxia-induced mRNA expressions of HIF-1α and OPN and In vitro radiosensitization by tirapazamine in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells
- VernacularTitle:替拉扎明调节乏氧诱导鼻咽癌细胞HIF-1α和OPN mRNA的表达及其对放射增敏的作用
- Author:
Xu PENG
1
;
Huang JIAN-MING
;
Ren YUAN
;
Zha XIAO
;
Deng BI-FANG
;
Wu JUN-HUI
;
Lang JIN-YI
Author Information
1. 广西医科大学
- Keywords:
Tirapazamine;
nasopharyngeal carcinoma;
irradiation;
HIF-1α;
osteopontin
- From:Chinese Journal of Cancer
2010;29(2):132-136
- CountryChina
- Language:Chinese
-
Abstract:
Background and Objective: Combined hypoxic cytotoxic drugs and chemoradiotherapy is an important mean of oncotherapy, and tirapazamine (TPZ) is one of the most remarkable drugs. It has been shown that TPZ has a synergistic effect with radiotherapy on tumor cells, but whether TPZ would down-regulate the expression of the hypoxia-induced genes has not been reported. This study was to investigate the hypoxiainduced expression of hypoxia inducible factor-1α (HIF-1α) and osteopontin (OPN) mRNA in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells and the radiosensitization of TPZ, a hypoxia-specific drug, on HNE-1 and CNE-1 cells in vitro. Methods: The IC_(50) values of TPZ for HNE-1 and CNE-1 cells were measured using MTT assay, and the expression of HIF-1α and OPN mRNA in HNE-1 and CNE-1 cells was determined using RT-PCR under aerobic and hypoxic conditions, respectively. The survival rates of HNE-1 and CNE-1 cells treated with or without TPZ at IC_(10) in the presence or absence of oxygen for 6 h were determined using colony forming assay following exposure to 1-6 Gy of ~(60)Co radiation, and the dose-survival curves were plotted and the values of D_0, D_q and SER were calculated as a singlehit multitarget model. Results: The IC_(50) values of TPZ were 34.81 μmol/L and 35.02 μmol/L in HNE-1 and CNE-1 cells under aerobic condition, and 30.20 μmol/L and 28.48 μmol/L under hypoxic condition. The expressions of HIF-1α and OPN mRNA were reduced by TPZ in HNE-1 cells, but not in CNE-1 cells under hypoxic condition. The values of D_0 and D_q in HNE-1 and CNE-1 cells following irradiation under aerobic and hypoxic conditions were 0.89 Gy, 0.28 Gy and 0.72 Gy, 0.68 Gy, and 1.47 Gy, 0.44 Gy and 0.95 Gy,0.56 Gy, respectively. The values of D_0 and D_q for HNE-1 and CNE-1 cells treated with TPZ under hypoxic condition following irradiation were 0.66 Gy,0.21 Gy and 0.85 Gy, 0.79 Gy, respectively. Conclusion: TPZ would downregulate hypoxia-induced expression of HIF-1α and OPN mRNA of HNE-1 cells and radiosensitize the HNE-1 cells but not CNE-1 cells, and act as a hpoxia modifier.
