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1,3-Bis(2-chloroethyl)-1-nitrosourea enhances the inhibitory effect of Resveratrol on 5-fluorouracil sensitive/resistant colon cancer cells

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World Journal of Gastroenterology 2013年第42期19卷 7374-7388页

作者： Dipon Das ranjan preet Purusottam Mohapatra Shakti ranjan Satapathy Chanakya Nath Kundu Cancer Biology Division KIIT School of BiotechnologyKIIT UniversityBhubaneswarOdisha 751024India

AIM:To study the mechanism of 5-fluorouracil(5-FU)resistance in colon cancer cells and to develop strategies for overcoming such resistance by combination ***:We established and characterized a 5-FU resistance(5-FU-R)cell line derived from continuous exposure(25μmol/L)to 5-FU for 20 wk in 5-FU sensitive HCT-116 *** proliferation and expression of different representative apoptosis and anti-apoptosis markers in 5-FU sensitive and 5-FU resistance cells were measured by the MTT assay and by Western blotting,respectively,after treatment with Resveratrol(Res)and/or 1,3-Bis(2-chloroethyl)-1-nitrosourea(BCNU).Apoptosis and cell cycle arrest was measured by 4',6'-diamidino-2-phenylindole hydrochloride staining and fluorescence-activated cell sorting analysis,*** extent of DNA damage was measured by the Comet *** measured the visible changes in the DNA damage/repair cascade by Western ***:The widely used chemotherapeutic agents BCNU and Res decreased the growth of 5-FU sensitive HCT-116 cells in a dose dependent *** application of BCNU and Res caused more apoptosis in5-FU sensitive cells in comparison to individual *** addition,the combined application of BCNU and Res caused a significant decrease of major DNA base excision repair components in 5-FU sensitive *** established a 5-FU resistance cell line(5-FU-R)from 5-FU-sensitive HCT-116(mismatch repair deficient)cells that was not resistant to other chemotherapeutic agents(e.g.,BCNU,Res)except *** 5-FU resistance of 5-FU-R cells was assessed by exposure to increasing concentrations of 5-FU followed by the MTT *** was no significant cell death noted in5-FU-R cells in comparison to 5-FU sensitive cells after5-FU *** resistant cell line overexpressed anti-apoptotic[e.g.,AKT,nuclear factorκB,FLICE-like inhibitory protein),DNA repair(e.g.,DNA polymerase beta(POL-β),DNA polymerase eta(POLH),protein Flap endonuclease 1(FEN1),DNA dam

关键词： 5-fluorouracil 1,3-Bis(2-chloroethyl)-1-nitrosourea Resveratrol Colon cancer Combination therapy

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