| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Hypoxia-inducible factor-1α(HIF-1α) is a key regulator of cellular response to hypoxia and has been suggested as playing an important role in tumor progression and metastasis trough activation of various genes that are linked to regulation of angiogenesis, erythropoiesis, energy metabolism, and so on. In this project, we tried to clarify the importance of HIF-1α in oral cancer therapies as a molecular target. At first, we tried to estimate HIF-1 activation capacities of several oral cancer cell lines (HSC2, HSC3, HSC4, Ca9-22, KOSC2, KB) and cervical cancer cell line (HeLa) under hypoxic or hypoxia mimicking conditions : 1-10% pO_2 or various concentration of CoCl_2 for 4〜96 hrs. As a result, we found differential responses to hypoxia among these cell lines. In these cell lines, HeLa showed most prominent induction of HRE-luciferase activity by transfection assay. On the other hand, HSC2 and HSC3 were best, KOSC2 and Ca9-22 were moderate, and KB and HSC4 were weakest among oral cancer cell lines. Therefore we chose HSC2 and HeLa cells for HIF-1 inhibition experiments as follows. Among several compounds we tested, we found Irsogladine maleate as a dose-dependent regulator of HIF-1 transactivation function : Irsogladine upregulated HRE-luciferase activities in a treated range 1-10nM, but suppressed to 50% of their activities at more than 1μM concentrations under hypoxic conditions. In conclusion, we could find the possibility of HIF-1 as a molecular target for anti-cancer therapy.
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