重组Canstatin蛋白联合氟尿嘧啶治疗裸鼠结肠癌移植瘤实验研究.docVIP

重组Canstatin蛋白联合氟尿嘧啶治疗裸鼠结肠癌移植瘤实验研究 　　【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2~3 mm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制，瘤体质量明显低于对照组(P 　　【关键词】结肠癌；血管生成；血管生成抑制剂；Canstatin蛋白 　　?? 　　Efficacy of recombinant canstatin protein plus fluorouracil in treatment of colon cancer 　　 　　MA YAN,WANG Li,JIAO Dong-xiao,et al.The First Affiliated Hospital of Nanhua University,Hunan421001,China 　　? 　　【Abstract】 Objective To study the anti-tumor effects of recombinant canstatin protein plus 5-fluorouracil(5-FU)on colon cancer in order to develop a new treatment modality.Methods Tumor xenografts were established by subcutaneous inoculation of 1×107 SW-480 colon cancer cells into the right flanks of 30 nude mice.When the tumors reached 2~3 mm in diameter,mice were randomly divided into 6 groups.All the agents were injected intraperitoneally.During the treatment,the subcutaneous tumors were measured by compasses and caliper every 3 or 4 days.At the end of the experiment,all the tumors were resected and both routine pathological and immunohistochemical staining examinations were performed to observe the drug toxicity and intratumoral microvescular density(MVD).Results ①In every treatment group tumor growth was suppressed significantly.Intraperitoneal injection of canstatin low-dose group,canstatin high-dose group,5-FU group,5-FU group+ low-dose canstatin group,5-FU group+ high-dose canstatin group resulted in a significant inhibition of the growth of SW-480 in vivo compare with that of control group(P[1,2]。随着分子生物学的发展,利用DNA重组和基因转移技术的结肠癌基因治疗成为极有发展前景的治疗方法。在迄今发现的的多种抗肿瘤药物中,血管生成抑制剂以其显著的抗肿瘤效果吸引了众多的研究,Canstatin是继血管抑素和内皮抑素后新发现的一种内源性血管生成抑???剂[3-6]。 体内外实验表明,Canstatin具有抑制新生血管生成，抑制异种移植人前列腺癌和人肾癌的生长的作用,疗效甚至强于内皮抑素,引起人们普遍关注。但是,Canstatin对人结肠癌的作用如何,尚未见报道,其与传统化疗药物联合应用的疗效亦有待阐明。笔者在既往研究中,成功克隆了Canstatin基因[7],并表达出活性重组人Canstatin蛋白,在此基础上,笔者探讨了Canstati