重组Ｃａｎｓｔａｔｉｎ蛋白联合氟尿嘧啶治疗裸鼠结肠癌移植瘤的实验研究

《重组Ｃａｎｓｔａｔｉｎ蛋白联合氟尿嘧啶治疗裸鼠结肠癌移植瘤的实验研究》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、重组Ｃａｎｓｔａｔｉｎ蛋白联合氟尿嘧啶治疗裸鼠结肠癌移植瘤的实验研究作者：马艳　王力　焦东晓　王淑芬　　【摘要】目的探讨血管生成抑制剂Canstatin与细胞毒药物氟尿嘧啶(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(1×107/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)。结果①各试验组肿瘤的生长明显受到抑

2、制，瘤体质量明显低于对照组(P<0．01)。5-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%。②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生长

3、,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　　12　　【Abstract】ObjectiveTostudytheanti-tumoreffectsofrecombinantcanstatinproteinplus5-fluorouracil(5-FU)oncoloncancerinordertodevelopanewtreatmentmodality.MethodsTumorxenograftswereestablishedbysubcutaneousinoculationof1×107S

4、W-480coloncancercellsintotherightflanksof30nudemice.Whenthetumorsreached2~3mmindiameter,micewererandomlydividedinto6groups.Alltheagentswereinjectedintraperitoneally.Duringthetreatment,thesubcutaneoustumorsweremeasuredbycompassesandcaliperevery3or4days.Attheendoftheexperiment,allthetumorswer

5、eresectedandbothroutinepathologicalandimmunohistochemicalstainingexaminationswereperformedtoobservethedrugtoxicityandintratumoralmicrovesculardensity(MVD).Results①Ineverytreatmentgrouptumorgrowthwassuppressedsignificantly.Intraperitonealinjectionofcanstatinlow-dosegroup,canstatinhigh-dosegr

6、oup,5-FUgroup,5-FUgroup+low-dosecanstatingroup,5-FUgroup+high-dosecanstatingroupresultedinasignificantinhibitionofthegrowthofSW-480invivocomparewiththatofcontrolgroup(P<0．05).Theanti-tumoreffectofcanstatinplus5-FUwassignificantlysuppressedthetumorgrowth.Attheendoftheexperiment,thesizeoft

7、umorsincombinationgroupwasthe12lowest(P<0．05),withthehighesttumorsuppressionrateof74．76%and82．04%.②TheimmunohistochemicalexaminationshowedthattheMVD5-FUgroup+canstatinlow-dosegroup(22．6±3．6)、5-FUgroup+canstatinhigh-dosegroup(15．0±2．8)wassignificantlyl