重组Ｃａｎｓｔａｔｉｎ蛋白联合氟尿嘧啶治疗裸鼠结肠癌移植瘤.doc

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1、重组Canstatin蛋白联合氟尿囉噪治疗裸鼠结肠癌移植瘤作者：马艳王力焦东晓王淑芬【摘要】目的探讨血管生成抑制剂Canstatin与细胞毒药物氟尿喘噪(5-FU)联合应用治疗结肠癌的效果，以期探索结肠癌治疗新途径。方法结肠癌SW-480细胞(IX107/只)注射到30只裸鼠皮下，建立结肠癌皮下移植瘤模型。当肿瘤长至2~3mm时，随机分6组。给药途径均为腹腔注射给药。治疗期间，定期用圆规和游标卡尺测量皮下移植瘤大小。疗程结束时，取下瘤体，常规病理切片，观察药物毒性反应,CD31免疫组化染色，检测肿瘤内微血管密度(MVD)o结果①各试验组肿瘤的生长明显受到抑制，瘤体

2、质量明显低于对照组(P<；0.01)o5-FU+Canstatin组低、高浓度联合治疗组抑瘤作用较对照组明显增强(P<；0.05),其瘤重抑制率分别为74.76%和82.04%o②免疫组化：5-FU+Canstatin组低浓度组(22.6±3.6)和5-FU+Canstatin组高浓度组(15.0±2.8)治疗小鼠肿瘤组织内MVD显著低于对照组(36.4±5.6)和5-FU治疗组(31.2±4.0)(P<；0.05),而5-FU治疗组与对照组间差异无统计学意义;③不良反应：各实验组未观察到明显毒性反应。结论重组人Canstatin蛋白能有效抑制人结肠癌

3、生长，无明显毒副作用，为结肠癌治疗提供了新的有力的治疗方法。【关键词】结肠癌；血管生成；血管生成抑制剂；Canstatin蛋白[Abstract]ObjectiveTostudytheanti-tumoreffectsofrecombinantcanstatinproteinplus5~fluorouraci1(5-FU)oncoloncancerinordertodevelopanewtreatmentmodality・MethodsTumorxenograftswereestablishedbysubcutaneousinoculationof1X107SW-

4、480coloncancercellsintotherightflanksof30nudemice・Whenthetumorsreached2~3mmindiameter,micewererandomlydividedinto6groups.Alltheagentswereinjectedintraperitoneal1y.Duringthetreatment,thesubcutaneoustumorsweremeasuredbycompassesandcaliperevery3or4days.Attheendoftheexperiment,allthetumor

5、swereresectedandbothroutinepathologicalandimmunohistochemicalstainingexaminationswereperformedtoobservethedrugtoxicityandintratumoralmicrovesculardensity(MVD)・ResuIts①Ineverytreatmentgrouptumorgrowthwassuppressedsignificantly.Intraperitoneedinjectionofcanstatinlow-dosegroup,canstatinh

6、igh-dosegroup,5-FUgroup,5-FUgroup+low-dosecanstatingroup,5~FUgroup+high-dosecanstatingroupresultedinasignificantinhibitionofthegrowthofSW-480invivocomparewiththatofcontrolgroup(P<；0・05).Theanti—tumoreffectofcanstatinplus5~FUwassignificantlysuppressedthetumorgrowth.Attheendoftheexper

7、iment,thesizeoftumorsincombinationgroupwasthelowest(P&It；0.05),withthehighesttumorsuppressionrateof74.76%and82.04%.②TheimmunohistochemicalexaminationshowedthattheMVD5-FUgroup+canstatinlow-dosegroup(22・6+3・6)、5-FUgroup+canstatinhigh-dosegroup(15・0±2・8)wassignificantlylowerthanthatinNSg

8、roup(