[Upregulation of vascular endothelial growth factor by peroxide in human colon cancer].

ABSTRACT

OBJECTIVE: To clarify the possible effect of reactive oxygen species such as hydrogen peroxide on progression of human colorectal cancer. METHOD: Human colon carcinoma cell lines, L174T and HCT8, were treated with low concentration of hydrogen peroxide (10(-5) mol/L, 10(-7) mol/L and 10(-9) mol/L, possessed no effect on cancer cell growth) for 24 hours before being co-cultured with human endothelial cell line ECV-304. The migration of ECV-304 induced by cancer cells was calculated and the expression of vascular endothelial growth factor (VEGF) in cancer cells was determined using RT-PCR and ELISA. Dactinomycin (1.5 microg/ml) was applied to block the transcription of cancer cell so as to observe the effect site of cell. Finally the activity of NF-KappaB of cancer cells was estimated using laser scanning cytometry. RESULTS: Exogenous hydrogen peroxide of low concentration promoted the migration of endothelial cell induced by colon cancer cell. When the concentration of H(2)O(2) was 10(-5) mol/L, the average number of migration of endothelial cell induced by LS174T was 202.6 +/- 70.2, higher than the value of 154.6 +/- 37.9 when no H(2)O(2) was given (t = 3.4751, P = 0.0083). When the concentration of H(2)O(2) was 10(-5) mol/L, the average number of migration of endothelial cell induced by HCT8 was 145.4 +/- 65.3, higher than the value of 113 +/- 72.7 when no H(2)O(2) was given (t = 4.4183, P = 0.0084). The expression of vascular endothelial growth factor in cancer cells was enhanced to a certain degree, which could be blocked by Dactinomycin. And the half-time of VEGF mRNA was not prolonged by treatment with hydrogen peroxide. The activity of NF-KappaB of both colon carcinoma cell lines was at a higher level after being treated with hydrogen peroxide for 24 hours. CONCLUSION: Hydrogen peroxide increases vascular endothelial growth factor expression in colon cancer cell, and it is possible that such reactive oxygen species as hydrogen peroxide facilitates development of colon cancer.