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| 1 | 1,3-Bis(2-chloroethyl)-1-nitrosourea enhances the inhibitory effect of Resveratrol on 5-fluorouracil sensitive/resistant colon cancer cells显示文摘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 treatment.METHODS: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 cells.The 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,respectively.The extent of DNA damage was measured by the Comet assay.We measured the visible changes in the DNA damage/repair cascade by Western blotting.RESULTS:The widely used chemotherapeutic agents BCNU and Res decreased the growth of 5-FU sensitive HCT-116 cells in a dose dependent manner.Combined application of BCNU and Res caused more apoptosis in5-FU sensitive cells in comparison to individual treatment.In addition,the combined application of BCNU and Res caused a significant decrease of major DNA base excision repair components in 5-FU sensitive cells.We 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.The 5-FU resistance of 5-FU-R cells was assessed by exposure to increasing concentrations of 5-FU followed by the MTT assay.There was no significant cell death noted in5-FU-R cells in comparison to 5-FU sensitive cells after5-FU treatment.This 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 damage-binding protein 2(DDB2)]and 5-FU-resistance proteins(thymidylate synthase)but under expressed pro-apoptotic proteins(e.g.,DAB2,CK1)in comparison to the parental cells.Increased genotoxicity and apoptosis were observed in resistant cells after combined application of BCNU and Res in comparison to untreated or parental cells.BCNU increased the sensitivity to Res of 5-FU resistant cells compared with parental cells.Fifty percent cell death were noted in parental cells when 18μmol/L of Res was associated with fixed concentration(20μmol/L)of BCNU,but a much lower concentration of Res(8μmol/L)was needed to achieve the same effect in 5-FU resistant cells.Interestingly,increased levels of adenomatous polyposis coli and decreased levels POL-β,POLH,FEN1 and DDB2 were noted after the same combined treatment in resistant cells.CONCLUSION:BCNU combined with Res exerts a synergistic effect that may prove useful for the treatment of colon cancer and to overcome drug resistance. | Dipon Das Ranjan Preet Purusottam Mohapatra Shakti Ranjan Satapathy Chanakya Nath Kundu | 2013 | World Journal of Gastroenterology2013，19，42： | 4 |
| 2 | Two-phase anaerobic digestion of water hyacinth or urban garbage显示文摘 | CHANAKYA H N BORGAON KARS RAJAN M G C | 1992 | Bioresource Technology1992，42，： | 1 |
| 3 | Solidphase biogas production with garbage or water hyacinth 显示文摘 | CHANAKYA H N BORGAONKAR S MEENA G | 1993 | Bioresour Technol1993，46，： | 1 |
| 4 | Synthetic Hydrotalcite:United States显示文摘 | Chanakya M Plum B | 1990 | 02-271990，0227，： | 1 |
| 5 | Fermentation properties of agro-residues, leaf biomass and urban market garbage in a solid phase biogas fermenter 显示文摘 | Chanakya H N Srikumar K G Modak V | 1999 | Biomass and Bioenerg v1999，16，6： | 1 |
| 6 | Two - phase anae- robic digestion of water hyacinth or urban garbage 显示文摘 | Chanakya H N Sushama B Rajan M G C | 1992 | Bioresource Technology1992，42，2： | 1 |
| 7 | Anaerobic retting of banana and areca- nut wastes in a plug flow digester for recovery of fiber, biogas and compost显示文摘 | Chanakya H N Sreesha M | 2012 | Energy for Sustainable Development2012，16，2： | 1 |
| 8 | Solid-phase biogas production with garbage or water hyacinth显示文摘 | CHANAKYA H N BORGAONKAR S MEENA G | 1993 | Biore- source Technology1993，46，3： | 1 |
| 9 | Biomethanation of herbaceous biomass residues using 3-zone plug flow like digestions-A case study from India显示文摘 | Chanakya H N VReddy B V Jayan Modak | 2009 | Renewable Energy2009，34，2： | 1 |
| 10 | Microscale anaerobic digestion of point source components of organic fraction of municipal solid waste显示文摘 | Chanakya H N Isha Shanma Ramachandra T V | 2009 | Waste Management2009，29，4： | 1 |
| 11 | Two-phase anaerobic digestion of water hyacinth or urban garbage 显示文摘 | CHANAKYA H N SUSHAMA B RAJAN M G C | 1992 | Bioresource Technology1992，42，： | 1 |
| 12 | Biomethanation of herbaceous biomass residues using 3-zone plug flow like digesters-A case study from India显示文摘 | H N Chanakya B V VReddy Jayant Modak | 2009 | Renewable Energy2009，，34： | 1 |
| 13 | Anaerobic retting of banana and arecanut wastes in a plug flow digester for recovery of fiber, biogas and compost显示文摘 | Hoysall N. Chanakya Malayil Sreesha | 2012 | Energy for Sustainable Development2012，，2： | 1 |
| 14 | Biomethanation of herbaceous biomass residues using 3-zone plug flow like digestions-A case study from India显示文摘 | Chanakya H N VReddy B V Jayan Modak | | 0，，02： | 1 |
| 15 | Microscale anaerobic digestion of point source components of organic fraction of municipal solid waste显示文摘 | Chanakya H N Isha Sharma Ramachandra T V | | 0，，04： | 1 |
| 16 | Solid-phase biogas production with garhage or water hyacinth显示文摘 | Chanakya H N Sushama B Meena G Jagadish K S et a | 1993 | Bioresource Technology1993，46，3： | 1 |
| 17 | Fermentation properties of agro-residues, leaf biomass and urban market garbage in a solid phase biogas fermenter显示文摘 | Chanakya H N Srikumar K G Anand V | 1999 | Biomass and Bioenergy1999，16，6： | 1 |
| 18 | Solid-phase biogas production with garbage or water hyacinth显示文摘 | Chanakya H N Bobgaonka B S Meena G | 1993 | Bioresour Technol1993，46，： | 1 |
| 19 | Micro- scale anaerobic digestion of point source components of organic fraction of municipal solid waste显示文摘 | Chanakya H N Isha Sharma Ramachandra T V | 2009 | Waste Man- agement2009，29，4： | 1 |
| 20 | Solid-phase biogas production with garbage or water hyacinth显示文摘 | Chanakya H N Bobgaonka B S Meena G | 1993 | Bioresour Technol1993，46，： | 1 |
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