|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Hypoxic response proteins, including VEGF, iNOS, is required for enlargement of solid cancer tumors. Expression levels of these proteins are tightly regulated by hypoxia inducible factor-1 (HIF-1) at the transcriptional level. To develop the efficient cancer gene therapy, we tested the effect of HIF-1 gene on cancer cell growth.
At first, we found that p53 expression efficiently inhibited the VEGF expression and HIF-1 activity. This effect of p53 was not seen when mutated p53 was used. Furthermore, when p53-null Hep3B cells were transplanted into nude mouse, tumor size, angiogenesis, VEGF expression was markedly increased, whereas it was significantly reduced when p53-null Hep3B cell were used. These results indicated that abnormal p53 activated HIF-1 activity, increased VEGF expression, which in turn, increase the tumor growth rate.
We also found that gene transfection of HIF-1α gene protected hypoxic cell death, and conversely, transfection of anti-sence HIF-1α enhanced hypoxic cell death. These results suggested that anti-sence HIF-1α DNA is a useful tool for anti-cancer gene therapy.