MAPK／ERK信号转导通路在白藜芦醇抑制A431细胞株裸鼠移植瘤生长中的作用机制研究  

Roles of MAPK/ERK signaling pathway in the growth inhibition of an established A431 xenograft tumor in nude mice by resveratrol

作　　者：郝玉琴[1] 黄维星[2] 宁晓洪[1] 冯红霞[1] 张国惠[1] 李衡贵[1] 郝春光[3] 

机构地区：[1]内蒙古医学院第三附属医院皮肤科,包头014010 [2]内蒙古医学院第三附属医院神经内科,包头014010 [3]内蒙古医学院第三附属医院实验中心,包头014010

出　　处：《中华皮肤科杂志》2013年第4期248-252,共5页Chinese Journal of Dermatology

基　　金：内蒙古自治区自然科学基金（2011MS1148）

摘　　要：目的探讨白藜芦醇对人皮肤鳞状细胞癌（简称鳞癌）A431细胞株裸鼠移植瘤生长的影响。方法取对数生长期A431细胞株接种于Balb／c（nu／nu）裸鼠左腋下造模，7—8d后将A431裸鼠移植瘤模型按随机数字表法分为空白组、阴性对照组（生理氯化钠溶液组）、环磷酰胺（cTx）阳性对照组、白藜芦醇高、中、低剂量组，每组10只。通过终末瘤质量计算白藜芦醇的抑瘤率，观察各组移植瘤组织病理形态学变化，原位末端标记技术检测细胞凋亡，Western印迹检测各组移植瘤组织中P—ERK、p53、半胱氨酸天冬氨酸蛋白酶3（caspase3）的表达。SPSSl3．0统计软件对结果进行方差分析及Pearson相关分析。结果CTX组、白藜芦醇高、中、低剂量组、阴性对照组、空白组裸鼠移植瘤体积分别为（1153．56±255．41）、（1001．69±115．08）、（1206．80±175．88）、（1342．28±211．12）、（1642．34±225．85）、（1564．32±156．49）mm2，各组差异有统计学意义（F=16．00，P〈0．05）；各组瘤质量差异亦有统计学意义（F=19．15，P〈0．05），白藜芦醇高、中、低剂量组抑瘤率分别为45．57％、37．97％、15．51％。CTX组、白藜芦醇高、中、低剂量组、阴性对照组、空白组肿瘤组织的凋亡指数分别为36．79±8．86、33．15±6．00、18．09±3．92、10．53±4．20、3．87±1．63、2．73±1．61，白藜芦醇各组均高于阴性对照组及空白组（F=93．26，P〈0．05）。各组肿瘤组织中P—ERK／13肌动蛋白、p53／B肌动蛋白caspase3／B肌动蛋白比值经方差分析，F值分别为6．65、6．78、11．56，均P〈0．05，白藜芦醇各组P—ERK、p53、caspase3蛋白的表达均高于阴性对照组及空白组。经Pearson相关分析，裸鼠移植瘤P—ERK与p53、p53与easpase3表达具有显著相关性（r分别0．68和0．56，均P〈0．05）。结论白藜芦醇对A431荷瘤裸鼠移植瘤的生长具�Objective To evaluate the effect of resveratrol on the growth of an established A431 xenograft tumor in nude mice. Methods The model of human skin squamous cell carcinoma was established by inoculating A431 cells in log-phase growth into the left axillary fossa of Balb/c （nu/nu） nude mice. After 7 - 8 days, 60 mice bearing human A431 skin squamous cell carcinoma xenografts were randomly and equally divided into 6 groups： blank control group receiving no treatment, negative control group treated with intraperitoneal sodium chloride physiological solution, positive control group treated with intraperitoneal cyclophosphamide, high-, medium- and low-dose resveratrol groups treated with intraperitoneal resveratrol of 40, 20 and 10 μg per gram body weight per day, respectively. Tumor size was measured at a 4-day interval during the treatment course. After 14-day treatment, the mice were sacrificed. Xenograft tumors were removed from these mice and subjected to weight measurement, pathological examination by hematoxylin and eosin （HE） staining and apoptosis detection by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL）. Western blot was conducted to quantify the protein expression of apoptosis-related factors, including phosphorylated extracellular signal-regulated protein kinase （p-ERK）, p53 and caspase 3. Data were processed by SPSS 13.0 software, and statistical analysis was carried out by analysis of variance and Pearson correlation analysis. Results By the end of treatment, the xenograft tumor volume was （1153.56 ± 255.41） mm3, （1001.69 ± 115.08） mm3, （1206.80 ±175.88） mm3,（1342.28± 211.12） mm3, （1642.34 ± 225.85） mm3 and （1564.32 ± 156.49） mm3, and the weight was （1.84 ± 0.30） g, （1.72 ± 0.39） g, （1.96 ± 0.40） g, （2.67 ± 0.73） g, （3.16 ± 0.52） g, and （3.33 ± 0.59） g, respectively in the positive control group, high-, medium- and low-dose resveratrol group, negative control group and blank control group. Signi

关 键 词：癌 鳞状细胞 丝裂原激活蛋白激酶激酶类 肿瘤抑制蛋白质P53 细胞系 肿瘤 白藜芦醇 

分 类 号：R285.5[医药卫生—中药学]