去端肽胶原介导递送siRNA联合顺铂治疗前列腺癌的研究-论文.pdf

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1、·336·肿瘤防治研究2013年第40卷第4期doi：10．3971／j．issn．1000—8578．2013．04．005去端肽胶原介导递送siRNA联合顺铂治疗前列腺癌的研究王政华，朱志图StudyOilCombinedSystemicDeliveryofsiRNASpecifictoTumorMediatedbyAtelocolla-genandCisplatinagainstProstateCancerWANGZhenghua，ZHUZhituDepartmentofTumor，TheFirstA{{tliatedHospital，LiaoningMedicalUniversit

2、yJinzhou121001，ChinaCorrespondingAuthor：ZHUZhitu，E-mail：heroiheart@163．cornAbstract：ObjectiveToinvestigatedthetherapeuticefficacyandthesecurityofatelocollagen-mediatedmethodcombinedwithcisplatininprostatecancerthroughdeliveringsiRNAtocancerxenograftbyatelo—collagen．Bcl-x4_siRNA，combinedwithcisplat

3、in(CDDP)andmediatedbyatelocollagen，inapregrownsolidxenograftderivedfromprostatecancer．MethodsThenudemicewithxenograftfromPC-3cellswererandomlydividedintofourtreatmentgroups：tWOgroupsforlocalintraperitonealtumourinjectionandtheothertwogroupsforsystemicintravenousinjection．FoursiRNAstargetinghumanBc

4、l—xLmRNAweredesignedandcompoundedwithatelocollagen．ThenthecompoundofBcl—XLsiRNA／atelocollagen／CDDPorBcl-xLsiRNA／CDDPwererandomlyinjectedintothetreatmentgroups．Atregularintervals，thetumorvolumes，liverenzymeandrenalfunctionindifferentgroupsofmiceweremeasuredandevalua—ted．ResultsInintratumora1treatme

5、ntgroups，whencomparedwiththeinjectionofBc卜X】JsiRNA，Bcl—xLexpressionsinthePC-3xenograftwereeffectivelydownregulatedandtumorgrowthwasinhibitedbylocalinjectionofBcl-xLsiRNA／atelocollagen(P<0．001)．Inintravenoustreatmentgroups，Bcl—XLsiR—NA／atelocollagenalsoeffectivelyinhibitedtumorgrowthwhencomparedwit

6、htheinjectionofBcl-xLsiR—NA(P<0。001)．AndtherewerenosignificantlystatisticaldifferencesorseveresideeffectssuchasliverorrenaldamagebeforeorafterBcl—xisiRNA／atetocollageninbothgroups．ConclusionOurresultsindi—catethatsystemicdeliveryofsiRNAcombinedwithcisplatinviaatelocollagen，whichspecificallytargets

7、tumors，issafeandfeasibleforprostatecancertherapy．Keywords：siRNA；Prostatecancer；Atelocollagen；Cisplatin摘要：目的通过去端肽胶原向异体移植肿瘤递送siRNA，探讨去端肽胶原介导法联合顺铂在前列腺癌中的疗效及安全性。方法以Bcl-XLmRNA为靶点构建特异siRNA，提取去端肽胶原，制备siRNA／去端肽胶原复合物；以前列腺