环氧化酶2抑制剂塞来昔布对胰腺癌荷瘤裸鼠的治疗作用.doc

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1、环氧化酶2抑制剂塞来昔布对胰腺癌荷瘤裸鼠的治疗作用作者：刘江伟，张东辉，许永华，李开宗，窦科峰，张东，冯德元【摘要】　　目的探讨环氧化酶2（COX2）抑制剂塞来昔布对胰腺癌荷瘤裸鼠的治疗作用。方法构建胰腺癌荷瘤裸鼠模型,将成瘤裸鼠随机分为4组，分别给予纯水（对照组）和含有不同浓度（0.05%、0.1%、0.15%）的塞来昔布饮水，观测裸鼠肿瘤生长情况并测量不同时间的体积变化，于治疗28d后处死裸鼠，测瘤体重量，应用caspase3试剂盒检测caspase3活性，免疫组织化学法检测肿瘤增殖指数(PI)和微血管密度(MVD)。结果

2、治疗组裸鼠肿瘤体积的变化呈浓度依赖性和时效性；治疗28d后，治疗组瘤重量均明显低于对照组[(0.96±0.09)g、(0.78±0.06)g、(0.64±0.07)gvs(1.16±0.12)g，P<0.01)]；治疗组caspase3相对活性明显高于对照组(0.021±0.002、0.026±0.003、0.031±0.002vs0.006±0.001，P<0.01)。0.1%组、0.15%组的PI和MVD均明显低于对照组(P<0.05)；0.05%组的PI和MVD虽均低于对照组，但差异无统计学意义(P>0.

3、05)。结论COX2抑制剂塞来昔布可显著抑制荷胰腺癌裸鼠的肿瘤生长，其作用机制可能是通过提高caspase3活性来诱导细胞凋亡，通过抑制肿瘤细胞的增殖和新生血管的形成来发挥抗肿瘤效应，在临床上具有潜在的应用价值。【关键词】胰腺肿瘤；环氧化酶2；塞来昔布；裸鼠　　Abstract：ObjectiveToinvestigatethetherapeuticeffectsofcyclooxygenase2(COX2)inhibitorcelecoxibonnudemicebearinghumanpancreaticcancerxeno

4、graft.MethodsThenudemousemodelofpancreaticcancerwasestablishedwithhumanpancreaticcancercelllineBxPC3.Themicebearingtumorwererandomlydividedintofourgroups.Controlgroupwasprovidedwithpurewater,andtrialgroupswereprovidedwithwatercontaining500ppm,1000ppmand1500ppmcelecoxib,

5、respectively.Thetumorsizeandvolumeweremeasuredatdifferenttime.Thenudemiceweresacrificed28dayslaterafterthebeginningofthetreatment.Theweightofeachtumorwasweighed.Thecaspase3activitywasevaluatedusingacaspase3assaykit,theexpressionofproliferatingcellnuclearantigen(PCNA)an

6、dmicrovesseldensity(MVD)wereobservedusingimmunohistochemistry.ResultsThetumorvolumechangedwithdoseandtimedependentmanner.Thetumorweightsweresignificantlysmallerinthetrialgroups(celecoxibprovidedgroups)thaninthecontrolgroup(0.96±0.09g,0.78±0.06g,0.64±0.07gvs1.16±0.12g,P

7、<0.01).Thecaspase3activitywassignificantlyhigherinthecelecoxibprovidedgroupsthaninthecontrolgroup(0.021±0.002,0.026±0.003,0.031±0.002vs0.006±0.001,P<0.01).The6expressionsofPCNAandMVDweresignificantlylowerin1000ppmand1500ppmcelecoxibprovidedgroupsthaninthecontrolgr

8、oup(P<0.05).TheexpressionsofPCNAandMVDwerelowerin500ppmcelecoxibprovidedgroupsthaninthecontrolgroup,