抗疟药氯喹增强胃癌裸鼠移植瘤对顺铂的化疗敏感性.pdf

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1、·96·中华临床医师杂志f电子版)2014年1月第8卷第1期ChinJClinicians(ElectronicEdition)．January1．2014．Vol_8．No．1基础论著抗疟药氯喹增强胃癌裸鼠移植瘤对顺铂的化疗敏感性方念张慧卿刘小梅何波万以叶程海涛谢桂生【摘要】目的探讨抗疟药氯喹(CQ)增强顺铂(DDP)抑制胃癌SGC7901细胞裸鼠移植瘤生长的作用。方法建立胃癌SCJC7901细胞裸鼠异位移植瘤模型，将24只荷瘤鼠随机分为对照组、DDP组、CQ组和CQ+DDP组。腹腔注射给药，给药后每3日测量肿瘤体积。给药结束时处死裸鼠，剥离移植瘤

2、，称重。WesternBlot检测肿瘤组织beclin．1、LC3II／Icaspase3和P．gP表达，RT-PCR技术检测MDR1mRNA水平。结果与对照组相比，DDP组移植瘤生长缓慢，体积较小，抑瘤率为47．6％，而且Beclinl和LC3表达增加，LCI转换LCII增多。联合氯喹后，抑瘤率提高至84．7％(P<0．01)，LC3II／I比值下降；检测到caspase3蛋白水平升高，MDR1／P—gP表达下降(均P<0．05)。结论氯喹能增强胃癌裸鼠移植瘤对顺铂的化疗敏感性，这一作用可能与抑制自噬活性和下调多药耐药基因MDR1／P．gP的表达有

3、关。【关键词】顺铂；氯喹；胃肿瘤；抗药性，多药；移植瘤ChloroquinesensitizescisplatincytotoxicityinhumangastriccancerxenograftsFangNian’，ZhangHuiqing,LiuXiaomei,HeBo，Wan均ChengHaitao，XieGuisheng．’GastrointestinalDepartmentofInternalMedicine，TheFourthAfiliatedHospitalofNanchangUniversity,Nanchang330003，Chin

4、aCorrespondingauthor．"ZhangHuiqing,Email：hqzhang888@sina．com[Abstract]0bjectiveToinvestigatetheenhancedefectofcisplatinonchloroquineinSGC7901xenografs．MethodsThemodelsofSGC7901xenograRonathymicmousewereestablishedandrandomizedtofourgroupswithintraperitoneali~ectionofdiferentdru

5、gs：control，cisplatin(DDP)，chloroquine(CQ)andDDP+CQ．Drugswereinjectedonceevery3days，10timesinal1．ThetulTIOrvolumeweremeasuredduringtheprocessofdrugtherapy．Themiceweresacrificed3daysafterthelastinjection，andthentheweightoftumorweremeasured．WesternBlotwasperformedtodetecttheexpres

6、sionofbeclin-1，LC3II／I，Caspase3andP—gP，RT-PCRwasperformedtodetecttheexpressionofMDR1mRNA．ResultsComparedtogroupcontrol，thegrowthoftumorwerel~oreslowlyandthet1．1l~orvolumeweremuchsmalleringroupDDP,theinhibitionoftumorratewas47．6％：andtheexpressionofBeclinlandLC3wereup—regulated．A

7、ftercombinedwithCQ．theinhibitionoftumorratewasincreasedto84．7％(尸<0．o1)，andtheratiobetweenLC3II，1wasdecreased；theexpressionofMDR1andP—gPwerealsodown—regulated．ConclusionChloroquineCallenhancetheanti-tumorefectofcisplatinongastriccancerxenografts，inhibitionofautophagyanddown—regu

8、lationofMDR1／P—gPexpressionarepossiblytherelatedmechan