Expression of Hypoxia Inducible Factor-1α (HIF-1α) via Photodynamic Therapy in Oral Squamous Cell Carcinoma

In Taiwan, the problem of oral cancer in increasing, the increasing rate was the first of the cancer increasing rate. The death patient rate was over half of patient. The methods of treatment cancer were multiple various methods. The aids are elongation the life of patient and cure the disease. The main strategy of the treatment for oral cancer is surgery, but the facial defect resulting from surgery. Due to reduce the invasive treatment, photodynamic therapy (PDT) has been used in the treatment of many cancers, it is the potential therapy, and its advantage is that there is no significant facial defect. The Photodynamic therapy (PDT) is a kind of new developing treatment for cancer. 5-Aminolevulinic acid (ALA) is a novel photosensitizer for photodynamic therapy. We previously showed ALA-PDT can induce cytotoxicity in oral cancer cells. The mechanism for the ALA-PDT induced cytotoxicity is still unknown. Oxygen is the important quench of the three fundamental elements. The expression of hypoxia-inducible factor-1α (HIF-1α) is the regular of oxygen. Overexpressions of HIF-1α have induced the tumor growth and angiogenesis, and affect the treatment result of the cancer therapy, such as radiotherapy and chemotherapy. The PDT has induced the reactive oxygen species (ROS), in the procedure, the O2 was decreased and due to the hypoxia situation. We want to know if the situation was the main cause. That needs us to research. Overexpression of hypoxia-inducible factor-1α (HIF-1α) has been demonstrated in a variety of human cancers and found to be significantly associated with the tumor invasion, lymph node metastasis, clinical stage, survival rate, and prognosis of these cancers. What role is the HIF-1α in the ALA-PDT? In the past study, we found the expression of VEGF was induced with expression of HIF-1α during hypoxia. How to expression of VEGF in the ALA-PDT? In this study, the immunohistochemistry, Western blot analysis, and MTA assay will be used to investigate if the expression of HIF-1α correlates with the varied treatment results of PDT. And the expression of HIF-1α in 13 specimens of oral squamous cell carcinoma (OSCC). We were calculated and compared between the specimens. Then we treated the cell lines with ALA-PDT plus the inhibitor of the HIF-1α and the COX-2, free radical inhibitor and multiple drugs to research the expression of protein. n our study, we found the expressions of HIF-1α were increased with time follow, and induced the expressions of HO-1 and VEGF, then reduced the ALA-PDT-induced apoptosis. In CA9-22 and in SAS cell lines, we used the ALA-PDT treatment could induced the apoptosis. Apoptosis induced by ALA-PDT was both time- and dose-dependent. Pretreatment of cells with imidazole and histidine (singlet oxygen inhibitor) reduced the ALA-PDT-induced apoptosis. These results indicated that singlet oxygen was an important mechanism for ALA-PDT-induced apoptosis in cells lines. In the IHC, the expressions of HIF-1α had no significant finding with gender, age, tumor size, involved depth, tumor region and pathology. The expressions of HIF-1α in nucleus had significant different findings about the resistance to the photodynamic therapy. There is higher resistance to ALA-PDT in the lesion with over expression of HIF-1α. The HIF-1α protein maybe induce the target gene and protein expression to protect the cell survive. PDT combination with anti-HIF-1α treatment enhance the response.