塞来昔布对乳腺癌细胞株的放射增敏作用.pdfVIP

塞来昔布对乳腺癌细胞株的放射增敏作用

牛国梁;王辉;谢荣俊;张树友

【摘要】背景与目的:塞来昔布(celecoxib)能有效增强放射线对肿瘤的作用,但其作

用机制尚不清楚.本研究探讨塞来昔布对人乳腺癌MDA-MB-231细胞放射增敏的

作用机制.方法:取对数生长期MDA-MB-231细胞株2×106个,分为对照组、药物

组、照射组及实验组(照射线联合塞来昔布),流式细胞分析法(flowcytometry,FCM)

检测各组细胞凋亡率;克隆形成实验检测放射增敏作用;Westernblot法检测Akt、

pAkt蛋白表达.结果:实验组凋亡率[(31.20±1.27)%]显著高于照射组

[(17.99±1.01)%](t=14.01,P0.05);与照射组相比较,实验组反映放射敏感性的指标

准域剂量(Dq)、平均致死剂量(D0)、2Gy照射的存活分数(SF2)值均显著降低

(0.437vs1.175,1.874vs2.394,0.52vs0.79),放射增敏比(SERD0)为1.277;各组

Akt蛋白表达无明显差异,但塞来昔布能抑制pAkt的表达,而放射线能上调其表达,

两者联合使用对pAkt表达有明显抑制作用(P0.05).结论:塞来昔布对人乳腺癌

MDA-MB-231细胞有放射增敏作用,其可能的机制是阻断PI3K/Akt信号通路的活

化,从而提高乳腺癌放射敏感性.%Backgroundandpurpose:Celecoxibhas

beenreportedtosensitizetumorcellstoirradiation,butthemechanismof

theradiosensitizationisstillunclear.Thepurposeofthisexperimentwasto

investigatetheeffectofcelecoxibontheradiosensitivityofhumanbreast

cancercells.Methods:TheMDA-MB-231celllineinthelogarithmicphase

wasdividedinto4groups:thecontrolgroup,druggroup,radiationgroup

andthecasegroup(radiation+celecoxib).Theapoptosisratewasanalyzed

usingflowcytometry(FCM).Theradiosensitizationeffectwasdetected

usingcloneformationexperiment.AktandpAktproteinexpressionswere

detectedbyWesternblotmethod.Results:Apoptosisrateinthecase

groupwassignificantlyhigherthanthatoftheradiationgroup,at

(31.20±1.27)％and(17.99±1.01)％,respectively(P＜0.05).ThevaluesofDq,

D0andSF2inthecasegroupsignificantlydecreasedcomparedwiththose

intheradiationgroup.SERDOwasat1.277accordingtotheclonogenic

assay.CelecoxibinhibitedpAktexpression,whereasradiationincreased

pAktexpression,butbothcelecoxibandradiationinthecasegroup

significantlyinhibitedpAktexpression.Conclusion:Celecoxibobviouslyhas

aradiotherapysensitizationeffectonhumanbreastcancerMDA-MB-231

cell,andth