摘要
目的 观察阿维A联合克拉霉素对人口腔表皮样癌裸鼠移植瘤生长的影响,探讨药物对肿瘤抑制的作用机制.方法 用人口腔表皮样癌细胞建立裸鼠皮下移植瘤模型.采用随机双盲设计,将31只裸鼠随机分6组,对照组、安慰剂组、阿维A组、克拉霉素组、阿维A＋安慰剂组、阿维A＋克拉霉素组.对照组6只,余各组均为5只裸鼠.各组治疗3周后测量移植瘤体积和重量,用RT-PCR检测血管内皮生长因子（VEGF）和核转录因子κB（NF-κB）mRNA的表达.对移植瘤体进行病理学分析,采用免疫组化染色检测各组肿瘤中VEGF、细胞增殖指数Ki-67的表达及其微血管密度（MVD）.采用SPSS 19.0软件进行统计分析,计量资料的均数比较采用方差分析,组间两两比较采用LSD检验.结果 阿维A＋克拉霉素组瘤体体积、瘤体重量均低于其他5组,差异有统计学意义（均P＜ 0.05）.实时荧光定量PCR检测,阿维A＋克拉霉素组VEGF、NF-κB mRNA的表达均低于对照组、克拉霉素组、阿维A组,差异均有统计学意义（均P＜ 0.05）.免疫组化检测,与对照组、克拉霉素组、阿维A组相比,阿维A＋克拉霉素组VEGF表达率均下调（均P＜ 0.01）,着色浅;MVD显著降低（均P＜ 0.01）,微血管分布较稀疏;Ki-67阳性指数均降低（均P＜0.05）,肿瘤细胞增殖减少.结论 阿维A联合克拉霉素能协同抑制人口腔表皮样癌裸鼠移植瘤的生长,并下调VEGF表达,抑制血管生成和肿瘤增殖.
Objective To evaluate the effects of acitretin combined with clarithromycin on tumor growth in human oral epidermoid carcinoma xenografts in nude mice,and to investigate their antitumor mechanisms.Methods A cell line of human oral epidermoid carcinoma was subcutaneously inoculated into 31 Balb/c nude mice to establish a xenograft model of human skin tumor.Then,the nude mice were randomly classified into 6 groups according to a double blind protocol：control group （n =6） remaining untreated,placebo group （n =5） treated with wheat flour,acitretin group （n =5） treated with acitretin 7.2 mg/kg per day,clarithromycin group （n =5） treated with clarithromycin 100 mg/kg per day,acitretin ＋ placebo group （n =5） treated with both acitretin （7.2 mg/kg per day） and wheat flour,and acitretin ＋ clarithromycin group （n =5） treated with acitretin （7.2 mg/kg per day） and clarithromycin 100 mg/kg per day.All the drugs were intragastrically administrated once daily.After three weeks of treatment,mice were sacrificed and xenografts were removed.Then,the size and weight of xenografts were measured,and pathological analysis was conducted.Real time-PCR was performed to quantify the mRNA expressions of vascular endothelial growth factor （VEGF） and nuclear factor （NF）-κB,and immunohistochemistry was carried out to observe the expression of VEGF as well as to determine microvessel density （MVD） and Ki-67 proliferation index.By using the software SPSS 19.0,analysis of variance was performed for comparison of measurement data,and least significant difference （LSD） test for paired comparisons.Results Both the size and weight of xenografts in the acitretin ＋ clarithromycin group were significantly lower than those in the other groups （all P 〈 0.05）.Real-time fluorescence-based PCR revealed weaker mRNA expressions of VEGF and NF-κB in the acitretin ＋ clarithromycin group compared with the control group,clarithromycin group and acitretin group （all P 〈 0.05）.As immunohistoch
出处
《中华皮肤科杂志》
CAS
CSCD
北大核心
2015年第3期197-200,共4页
Chinese Journal of Dermatology
基金
福建省卫生厅医学创新课题（2011-CXB-11）
