慢性病毒介导RNA靶向干扰Bi-1抑制鼻咽癌细胞的增殖和生长

HumGeneTher2011Oct;22(10):1201-8.[IF:4.829]Lentivirus-mediatedRNAinterferencetargetingbaxinhibitor-1suppressesexvivocellproliferationandinvivotumorgrowthofnasopharyngealcarcinoma.LiXY,LaiYK,ZhangJF,LuoHQ,ZhangMH,ZhouKY,KungHF.1InstituteofBiochemistryandMolecularBiology,GuangdongMedicalCollege,Zhanjiang,Guangdong524023,China.广东医学院生物化学与分子生物学研究所

AbstractAbstractBaxinhibitor-1(Bi-1),ananti-apoptoticproteinthatbelongstotheBcl-2family,playsanimportantroleinthemitochondrialapoptosispathwaytosuppressBax-inducedapoptosis.Inseveralhumancancers,includingnasopharyngealcarcinoma,itsexpressionwasfoundtobeincreased;however,up-regulatedexpressionofthisproteinhasbeenlinkedtoincreasedcellproliferations.Inthisstudy,wedown-regulatedthegeneexpressionofBi-1innasopharyngealcarcinomacellsbyusingalentivirustransfectionsystempackedwithshorthairpinRNAtargetingBi-1andusedaninvivomodeltoassessitsefficacyasatargetinhumangenetherapy.Thedataindicatedthathumanmalignantnasopharyngealcarcinomacells,CNE-1andSUNE-1,transfectedwithlentiviralshorthairpinRNAtargetingBi-1grewmoreslowlyandshowedahigherdegreeofapoptosis.Moreover,thetumorigenicityofCNE-1wassignificantlysuppressedwheninoculatedmicewereintratumoricallyinjectedwiththesamevector.Takentogether,thesedataleadustoconcludethatBi-1playsacrucialroleinCNE-1tumorigenesisandthatBi-1maybeanoveltherapeutictargetfornasopharyngealcarcinoma.

摘要：Bax-1抑制剂（Bi-1）是Bcl-2一种家族抗凋亡蛋白，抑制原因Bax诱导线粒体凋亡通道起着重要作用。在各种人类癌症(包括鼻咽癌)中发现Bi-1蛋白质的增加。蛋白质表达的增加与细胞增殖有关。在这项研究中，我们使用靶向Bi-1的sh-RNA慢性病毒转移载体降低鼻咽癌细胞Bi-1基因表达。与此同时，我们评估了基因治疗药物在体内动物模型中的有效性。数据显示，转移包括靶向Bi-1的sh-RNA慢性病毒转移载体人类转移性鼻咽癌细胞株CNE-1和SUNE-1生长缓慢，凋亡增加。此外，在肿瘤中注射载体后，在小鼠体内接种疫苗CNE-1细胞株的致瘤性受到显著抑制。综上所述，通过这些数据，我们可以得到结果，Bi-1在CNE-1在致瘤性中起着重要作用。Bi-1可能是鼻咽癌的新治疗目标。