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The Involvement of Hypoxia-Inducible Factor- 1α in the Susceptibility to γ-rays and Chemotherapeutic Drugs of Oral Squamous Cell Carcinoma Cells

Issue: Vol.9, No.4 - October 2010

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Article Type: Manuscript

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  1. Dr Eri Sasabe
    Department of Oral Oncology, Kochi Medical School, Kochi University
  2. Xuan Zhou
  3. Dechao Li
  4. Naohisa Oku
  5. Tetsuya Yamamoto
  6. Tokio Osaki

The transcription factor hypoxia-inducible factor-1α (HIF-1α) is the key regulator that controls the hypoxic response of mammalian cells. The over-expression of HIF-1α has been demonstrated in many human tumors. However, the role of HIF-1α in the therapeutic efficacy of chemotherapy and radiotherapy in cancer cells is poorly understood. In this study, we investigated the influence of HIF-1α expression on the susceptibility of oral squamous cell carcinoma (OSCC) cells to chemotherapeutic drugs (cisdiamminedichloroplatinum and 5-fluorouracil) and γ-rays. Treatment with chemotherapeutic drugs and γ-rays enhanced the expression and nuclear translocation of HIF-1α, and the susceptibility of OSCC cells to the drugs and γ-rays was negatively correlated with the expression level of HIF-1α protein. The over-expression of HIF-1α induced OSCC cells to become more resistant to the anticancer agents, and down-regulation of HIF-1α expression by small interfering RNA enhanced the susceptibility of OSCC cells to them. In the HIF-1α knockdown OSCC cells, the expression of P glycoprotein, heme oxygenase-1, manganese-superoxide dismutase and ceruloplasmin were down-regulated and the intracellular levels of chemotherapeutic drugs and reactive oxygen species were sustained at higher levels after the treatment with the anticancer agents. These results suggest that enhanced HIF-1α expression is related to the resistance of tumor cells to chemo- and radio-therapy and that HIF-1α is an effective therapeutic target for cancer treatment.

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