Expression of hypoxia-inducible factor-1alpha (HIF-lalpha) and correlation with radiation resistance in human oral squamous cell carcinoma cell lines.

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The relationship between hypoxia-inducible factor (HIF)-1alpha and radiation resistance in tumor cells has been unknown. We examined the effects of 5 Gy radiation under normoxia on the expression of HIF-1alpha, apoptosis, and migration capacity of five human oral squamous cell carcinoma (OSCC) lines. Cells in all of the lines expressed HIF-1alpha mRNA, and radiation had no influence on gene transcription. Western blot analysis did not detect the p53 tumor suppressor, which induces apoptosis through HIF-1alpha degradation, either before or after radiation exposure. Numbers of apoptotic cells increased 72 h after irradiation in lines TT, Ca9-22, and SAS, indicating low transcriptional levels of HIF- lalpha, and levels of non-cleaved caspase-3, an executioner of apoptosis, and non-cleaved poly (ADP-ribose) polymerase (PARP), a marker of DNA damage early in apoptosis, decreased at the same time. On the other hand, radiation failed to induce apoptosis or to decrease levels of non-cleaved caspase-3 and PARP in lines IS-FOM and BSC-OF, which express HIF-1alpha at high levels. Cell lines IS-FOM and BSC-OF showed high migration capacity. The other cell lines showed low capacity. These results suggest that OSCC cells expressing a high level of HIF-1alpha are resistant to radiation.