异汉防己碱增强多药耐药肿瘤细胞对阿霉素的敏感性及其机制的论文

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1、异汉防己碱增强多药耐药肿瘤细胞对阿霉素的敏感性及其机制的论文异汉防己碱增强多药耐药肿瘤细胞对阿霉素的敏感性及其机制的论文【摘要】目的以k562/dox和mcf7/dox细胞为对象，探讨异汉防己碱对化疗药物阿霉素（dox）的增敏作用及其作用机制。方法采用mtt法检测异汉防己碱的内在细胞毒性及其对阿霉素的增敏作用，并以rf值评价其增敏效果。应用流式细胞术（fcm）检测细胞膜上pgp的表达以及细胞内dox和罗丹明123（rh123）的蓄积量。结果异汉防己碱在10μg/ml的无毒剂量可明显增强dox的细胞毒性。k

2、562/dox和mcf7/dox细胞膜上pgp均呈强阳性表达，但异汉防己碱对该pgp表达水平无明显影响。异汉防己碱可使k562/dox和mcf7/dox细胞内dox和rh123的荧光密度（fi）均明显增加，由此证明异汉防己碱可有效抑制pgp的功能。结论异汉防己碱可通过抑制pgp的功能而增强阿霉素的敏感性，从而有效逆转肿瘤细胞的多药耐药性（mdr），它可能成为有效多药耐药逆转剂的候选药物。【关键词】异汉防己碱；阿霉素；肿瘤细胞；多药耐药性abstract：objectivetoexplorethee

3、ffectandmechanismofisotetrandrinetoenhancedoxorubicin(dox)sensitivityofk562/doxandmcf7/doxcells.methodstheactivityofisotetrandrinetoenhancedoxorubicincytotoxicitywastestedusingmtt[3(4,5dimethylthiazol)2,5diphenyltetrazoliumbromide]assayandevaluatedbyth

4、ereversalfold(rf)values.thelevelofpglycoprotein(pgp)expressionandintracellularaccumulationofdoxorubicinandrhodamine123(rh123)wereassessedbyflowcytometry(fcm).resultsthedoxorubicininducedcytotoxicitywassignificantlypotentiatedbyisotetrandrinewiththeconcen

5、trationof10μg/ml.pgpwasexpressedinbothk562/doxcellsandmcf7/doxcells,butthelevelofpgpexpressionwasnotdistinctdifferenceattheabsenceorpresenceofisotetrandrine.theintracellularaccumulationofdoxandrh123wasincreasedinthepresenceofisotetrandrine,whichindicated

6、thatthefunctionofpgpwaseffectivelyinhibited.conclusionisotetrandrineexhibitedpotenteffectinthereversaloftumormultidrugresistance(mdr)byinhibitingthefunctionofpgpinvitro,suggestingthatitmaybeeacandidateofeffectivemdrreversingagentsincancerchemotherapy.keyw

7、ords：isotetrandrine;doxorubicin;tumorcells;multidrugresistanceintroductioncancermultidrugresistance(mdr)isoneofthemajorobstaclesforthesuccessofchemotherapy.itisrelatedtoa170kdaplasmamembraneprotein,pglycoprotein(pgp)[1].pgpfunctionsasanatpdependentdrugs

8、transporterwhichunilaterallytransportstheintracellulardrugsoutofthecells，therebyreducingdrugcytotoxicity.sochemotherapydrugsinconjunctionwithapgpinhibitoratthetimeoftumortreatmentwillbetheeffectiveway