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Effects of tyrosine kinase inhibitor E7080 and eNOS inhibitor L-NIO on colorectal cancer alone and in combination 被引量:4

Effects of tyrosine kinase inhibitor E7080 and eNOS inhibitor L-NIO on colorectal cancer alone and in combination
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摘要 Objective:To investigate the effects of E7080 and N5-(1-iminoethyl)-L-ornithine dihydrochloride (L-NIO)on colorectal cancer alone and in combination.Methods:HT29 colorectal cancer cell line from Sap Institute was used.Real-time cell analysis (xCELLigence system) was performed to determine the effects of E7080 and L-NIO on colorectal cell proliferation.While apoptosis was determined with Annexin V staining,and the effect of agents on angiogenesis was determined with chorioallantoic membrane (CAM) model.Results:We found that E7080 has a strong antiproliferative effect with an half maximum inhibition of concentration (IC50) value of 5.60×10-8 mol/L.Also it has been observed that E7080 showed antiangiogenic and apoptotic effects on HT29 colorectal cancer cells.Antiangiogenic scores of E7080 were 1.2,t.0 and 0.6 for 100,10 and 1 nmol/L E7080 concentrations,respectively.Furthermore,apoptosis has been detected in 71% of HT29 colorectal cancer cells after administration of 100 nmol/L E7080 which may indicate strong apoptotic effect.Meanwhile administration of L-NIO alone did not show any effect,but the combination of E7080 with L-NIO increased the antiproliferative,antiangiogenic and apoptotic effects of E7080.Conclusions:Results of this study indicate that E7080 may be a good choice in treatment of colorectal tumors.Furthermore the increased effects of E7080 when combined with L-NIO raise the possibility to use a lower dose of E7080 and therefore avoid/minimize the side effects observed with E7080. Objective:To investigate the effects of E7080 and N5-(1-iminoethyl)-L-ornithine dihydrochloride (L-NIO)on colorectal cancer alone and in combination.Methods:HT29 colorectal cancer cell line from Sap Institute was used.Real-time cell analysis (xCELLigence system) was performed to determine the effects of E7080 and L-NIO on colorectal cell proliferation.While apoptosis was determined with Annexin V staining,and the effect of agents on angiogenesis was determined with chorioallantoic membrane (CAM) model.Results:We found that E7080 has a strong antiproliferative effect with an half maximum inhibition of concentration (IC50) value of 5.60×10-8 mol/L.Also it has been observed that E7080 showed antiangiogenic and apoptotic effects on HT29 colorectal cancer cells.Antiangiogenic scores of E7080 were 1.2,t.0 and 0.6 for 100,10 and 1 nmol/L E7080 concentrations,respectively.Furthermore,apoptosis has been detected in 71% of HT29 colorectal cancer cells after administration of 100 nmol/L E7080 which may indicate strong apoptotic effect.Meanwhile administration of L-NIO alone did not show any effect,but the combination of E7080 with L-NIO increased the antiproliferative,antiangiogenic and apoptotic effects of E7080.Conclusions:Results of this study indicate that E7080 may be a good choice in treatment of colorectal tumors.Furthermore the increased effects of E7080 when combined with L-NIO raise the possibility to use a lower dose of E7080 and therefore avoid/minimize the side effects observed with E7080.
出处 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2013年第5期572-584,共13页 中国癌症研究(英文版)
关键词 E7080 N5-(1-iminoethyl)-L-ornithine dihydrochloride (L-NIO) colorectal cancer xCELLigence system tyrosine kinase (TK) E7080 N5-(1-iminoethyl)-L-ornithine dihydrochloride (L-NIO) colorectal cancer xCELLigence system tyrosine kinase (TK)
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