凋亡相关因子在白藜芦醇抑制人皮肤鳞状细胞癌裸鼠移植瘤生长中的调节作用  

Study of apoptosis related factors regulatory mechanism of resveratrol to human skin squamous cellcarcinoma A431 xenograft in nude mice

作　　者：郝玉琴[1] 黄维星[2] 冯红霞[1] 张国惠[1] 宁晓洪[1] 李衡贵[1] 郝春光[3] 李哲海[4] 

机构地区：[1]内蒙古医科大学第三附属医院皮肤科,包头014010 [2]内蒙古医科大学第三附属医院神经内科,包头014010 [3]内蒙古医科大学第三附属医院实验中心,包头014010 [4]内蒙古医科大学第三附属医院科研办公室,包头014010

出　　处：《中华医学杂志》2013年第6期464-468,共5页National Medical Journal of China

基　　金：内蒙古自治区自然科学基金（2011MS1148）

摘　　要：目的观察白藜芦醇（Res）对人皮肤鳞状细胞癌（鳞癌）A431裸鼠移植瘤生长的影响，探讨生存素（survivin）和半胱氨酸天冬氨酸蛋白酶3（caspase-3）在此过程中的调节作用。方法建立人皮肤鳞癌（A431）裸鼠移植瘤模型，按随机数字表法分为空白组、生理盐水阴性对照组、环磷酰胺（CTX）阳性对照组、Res高、中、低剂量组，每组10只，分别予以药物干预后处死荷瘤鼠。绘制移植瘤体积生长曲线；通过终末瘤质量，计算Res的抑瘤率；采用HE染色，观察各组移植瘤组织病理形态学变化；应用原位末端标记（TUNEL）技术检测细胞凋亡；采用Western印迹法检测Res对各组裸鼠移植瘤组织中survivin、caspase-3蛋白表达的影响。采用方差分析及Pearson相关分析对结果进行统计分析。结果治疗结束时，（1）CTX阳性对照组、Res高、中、低剂量组、阴性对照组、空白对照组移植瘤体积分别为（1154±255）、（1002±115）、（1207±176）、（1342±211）、（1642±226）、（1564±156）mm^3，瘤质量分别为（1．84±0．30）、（1．724±0．39）、（1．964±0．40）、（2．67±0．73）、（3．16±0．52）、（3．334±0．59）g，Res高、中、低剂量组瘤体积、瘤质量均低于阴性及空白对照组（均P〈0．05）；Res高、中、低剂量组抑瘤率分别为45．57％、37．97％、15．51％。（2）以上各组肿瘤组织的凋亡指数分另0为36．79％±8．86％、33．15％±6．00％、18．09％±3．92％、10．53％4±4．20％、3．87％±1．63％、2．7304±1．61％，Res高、中、低剂量组凋亡指数均高于阴性及空白对照组（均P〈0．05）。（3）以上各组肿瘤组织中survivin蛋白相对表达量分别为0．48±0．20、0．19±0．11、0．224±0．12、0．284±0．24、0．98±0．41、0．85±0．34；caspase-3蛋白相对表达量分别为0．42±0．09、0．31±0．10、0．314±0．07、0．224±0．08、Objective To explore the anti-tumor effects of resveratrol （Res） upon human skin squamous cell carcinoma A431 xenograft in nude mice and elucidate the regulatory mechanisms of survivin and caspase-3. Methods The model of human skin squamous cell carcinoma （ A431 ） xenograft in nude mice was established. And the animals were randomly divided into saline-negative control, cyelophosphamide （CTX） positive control, Res high-, medium- and low-dosage and blank control groups （n = 10 each）. After drug intervention, tumor-bearing mice were sacrificed. The tumor growth curve was plottedand the Res inhibition rate calculated by terminal tumor weight. The morphological changes of tumor cell among groups were observed by hematoxylin and eosin staining; cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL; the impact of Res upon the protein expressions of survivin and caspase-3 in tumor issues was observed by Western blot. Analysis of variance and Pearson＇s correlation were employed for statistical analyses. Results （1） By the end of treatment, the tumor volume of CTX, Res high-, medium-, low-dosage, saline-negative control and blank control groups were （ 1154 ±255 ）, （ 1002 ± 115 ）, （ 1207 ± 176 ）, （ 1342 ±211 ）, （ 1642 ± 226 ）, （ 1564 ± 156 ） mm3 respectively, and tumor weight of CTX, Res high-, medium-, low-dosage, saline-negative control and blank control groups （1.84±0.30）,（1.72 ± 0.39）, （1.96 ±0.40）, （2.67 ＋0.73）, （3. 16 ±0.52）, （3.33 ±0. 59） g respectively. Through analysis of variance, the tumor volume and weight of Res high-, medium-, low-dosage groups were smaller than those of saline-negative control and blank control groups （ all P 〈 0.05 ）. The inhibition rate of Res high-, medium- and low-dosage groups were 45. 57% , 37. 97% and 15. 51% respectively. （2） The apoptosis index of the above groups were 36.79% ± 8.86% ,33.15% ±6.00%, 18.09% ±3.92% , 10.53% ±4.20% ,3.87% ± 1.63%

关 键 词：癌 鳞状细胞 藜芦属 半胱氨酸天冬氨酸蛋白酶3 移植瘤 生存素 

分 类 号：R739.5[医药卫生—肿瘤]