[Upregulation of vascular endothelial growth factor by peroxide in human colon cancer].
OBJECTIVE
To clarify the possible effect of reactive oxygen species such as hydrogen peroxide on progression of human colorectal cancer.


METHODS
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.


CONCLUSIONS
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.
Zhu
Jianwei
J
Department of General Surgery, RuiJin Hospital Affiliated to Shanghai Second Medical University, Shanghai 200025, China.
Yu
Baoming
B
Ji
Yubao
Y
Zheng
Minhua
M
Li
Donghua
D
D003110:Colonic Neoplasms / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008222:Lymphokines / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D006861:Hydrogen Peroxide