Objective: To examine the effect of fractioned ionizing radiation on the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and multidrug resistance (MDR1) in human esophageal cancer cells.
Methods: The mRNA and protein levels of HIF-1alpha and MDR1 in esophageal caner EC9706 cells incubated in the presence of 150 micromol/L CoCl(2) were measured before and after the irradiation by quantitative RT-PCR and Western blotting, respectively. The chemosensitivity and radiosensitivity of the cells were analyzed by MTT assay and clone formation assay.
Results: MDR1 and HIF1alpha expressions were significantly up-regulated in the cells following hypoxia or irradiation (P<0.05). The surviving cell fraction in the exclusive irradiation group was significantly lower than that irradiation+hypoxia group (P<0.05). Compared with exclusive hypoxia group, MDR1 and HIF1alpha expressions were decreased significantly in irradiation+hypoxia group (P<0.05). HIF1alpha expression showed a positive correlation to MDR1 expression (P<0.01).
Conclusion: Hypoxia is an important factor to induce resistance to chemo- and radiotherapy. Low-dose fractioned irradiation can lower MDR1 and HIF1alpha expressions in esophageal cancer cells, which should be considered when combining radiotherapy chemotherapy for esophageal cancer patients.