低剂量阿霉素对胶质母细胞瘤的放射增敏作用研究

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1、上海交通大学硕士学位论文低剂量阿霉素对胶质母细胞瘤的放射增敏作用研究姓名：林清申请学位级别：硕士专业：肿瘤学指导教师：金冶宁20070501再给予大剂量的放射线照射，可以显著提高瘤细胞的杀伤率，而且细胞杀伤率的提高存在着时间依赖性，这个发现有望成为提高高分级胶质瘤的临床治疗疗效提供新的思路。关键词：放化疗，阿霉素，放射敏感性EnhancementofCellKillinginHumanGlioblastomaCellsTretedwith60C0RadiationCombinedwithLowDoseAdriamycinAbstract

2、PurposeandBackground:Thepurposeofourstudyistodefineincreasedresponseofglioblastomacellstoγ-rayirradiationwhendeliveredatexacttimeintervalsafterlowdosesofAdriamycin(ADR).PreviousstudieswiththehepatocellularcelllineHepG2showedenhancedcellkillingupto120-foldwhenlargerdoseso

3、fionizingradiation(>5Gy)weredeliveredexactly4hafteralowdoseofADR.Inthestudiesreportedhere,wedocumentedparalleleffectsinahumanglioblastomacellline.MaterialandMethods:HumanglioblastomacelllineU251,whichisresistanttoRadiation,wastreatedwithlowdoseADRfollowedbydifferentdoses

4、ofradiationatvarioustime-points.Cellsurvivalwasdeterminedbyclonogenicformationassay.Briefly,thecellsinexponentialgrowthphasewereincubatedwithADRfor1handconcentrationwas0.1ug/ml.Cellsinfreshmediumwerethenirradiatedwithgradeddoses(0,2,5and10Gy)ofγ-rayusingacobalt-60acceler

5、ator(75cGy/min)atcertaintimepoints(2,4,6,8,10and24h)afterADRtreatment.Thecellswerethentrypsinizedandre-platedinspecifiednumbersindrug-freemediumtodeterminethecolony-formingabilityafter16-dayincubation.Thecolonieswith>50cellswerecountedandtheresultswerenormalizedbythecyto

6、toxicityinducedbythedrugalone.Results:TherewerenosignificantdifferentsinU251cellswhencellswereirradiatedwith2Gycobalt-60aftervarioustimeintervalsaftertreatmentwithpulse(1hr)ofADR(0.1ug/ml).Howeverathigherdoses(5Gy,10Gy),therewasasignificantincreaseincellkillingwhentheint

7、ervalbetweenADRandirradiationwas4hto8h(p<0.05).Conclusion:Thereisatime-specificincreaseincellkillingwhenlargerdosesofionizingradiation(5Gyand10Gy)aredeliveredexactly4hto8h,especially6hafter1-hourpulseoflowdoseADR(0.1ug/ml).Weconcludethatanti-tumoreffectsofcombinedtreated

8、withionizingradiationandADRcanbesignificantlyenhancedwhenthetimeintervalbetweenapulseofADRandlargerfrac