亚麻木酚素联合硼替佐米诱导肺腺癌A549细胞凋亡的机制研究.pdf

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1、·248·呻善材JournalofChineseMedicinalMaterial,；第35卷第2期2012年2月·药理·亚麻木酚素联合硼替佐米诱导肺腺癌A549细胞凋亡的机制研究李先伟，杨解人(皖南医学院药理学教研室，安徽芜湖241001)摘要目的：探讨亚麻木酚素(SDG)联合蛋白酶体抑制剂硼替佐米(Bortezomib，Bor)对肺腺癌A549细胞凋亡的影响及其机制。方法：MTI"法检测细胞增殖；AnnexinV—FITC／PI双染流式细胞法和Hoeehst33258荧光染色法检测细胞凋亡；比色法检测半胱氨酸天冬氨酸蛋白酶．3(Caspase．3)活性；RealTimePCR检测Ca

2、spase．3、BCL-2、BAXmRNA的表达；WesternBlot检测BCL-2、Bax及p-JNK的蛋白表达。结果：SDG联合Bor能明显抑制细胞生长，上调Caspase一3活性，促进p-JNK、BAXmRNA和蛋白的表达，抑制BCL-2mRNA和蛋白的表达，诱导细胞凋亡。结论：SDG联合Bor可显著诱导肺腺癌A549细胞的凋亡，其机制可能与其激活JNK信号通路有关。关键词亚麻木酚素；硼替佐米；肺腺癌A549细胞；细胞凋亡中图分类号：R285．5文献标识码：A文章编号：100154(2012)02-0248-06EtfiectsofSecoisolariciresinolDigl

3、ucosideCombinedwithB0,rtezomibonInductionofApoptosisinLungCancerCallLineA549LIXian—wei，YANGJie—Fen(Departmentofpharmacology，WannanMedicalCollege，Wuhu241001，China)AbstractObjective：TostudytheinfluenceofSeeoisolariciresinolDiglucoside(SDG)combinedwithBortezomiboninductionofapoptosisinLungCancerCell

4、LineA549anditsrelativemechanisms．Methods：TheeffectonproliferationwasevaluatedbyMTras—say．ThecellapoptosiswasstudiedbyfloweytometryandHoeehst33342staining．ColorimetriemethodwasusedtOdetecttheactivityofCaspase-3．RealTimePCRwasusedtodetecttheexpressionofCaspase-3，BCL-2andBAXmRNA．Westernblotwasusedto

5、de-terminethechangeofp-INK，BCL-2andBAXproteinexpressioninA549cells．Results：Thecellgrowthwassignificantlysloweddownandthecellapoptosiswasinducedafterthecombinedtreatment,．MeanwhiletheCaspase．·3activityandtheexpressionofCaspase一3mRNAwereobviouslyincreased，theexpressionofBCL-2mRNAandproteinweresigni

6、ficantlydownregulatedandtheexpressionofBAX．p-JNKmRNAandproteinweresignificantlyupregulatedafterthecombinedtreatment．Conclusion：TheresultsdemonstratethatSDGcombinedwithBortezomibCansignificantlyinduceapoptosisofA549cells，itsmechanismsmaybeinvolvedinactivationoftheJNKpathway,．KeywordsSeeoisolaricir

7、esinolDiglueoside；Bortezomib；LungCancerCellLineA549；Apoptosis蛋白酶体抑制剂硼替佐米(Bortezomib，Bor)是癌的作用，未见文献报道，故本研究以A549细胞为新一类的抗肿瘤药物，能诱导多种肿瘤细胞和癌变研究对象，从细胞和基因水平探讨SDG联合Bor对细胞凋亡，显著增强某些化疗药物诱导肿瘤细胞凋非小细胞肺癌的效果和机制。亡的效果，而对于正常细胞的毒性相对较小⋯。但1材