Roles of MAPK/ERK signaling pathway in the growth inhibition of an established A431 xenograft tumor in nude mice by resveratrol
10.3760/cma.j.issn.0412-4030.2013.04.008
- VernacularTitle: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
- Author:
Yuqin HAO
;
Weixing HUANG
;
Xiaohong NING
;
Hongxia FENG
;
Guohui ZHANG
;
Henggui LI
;
Chunguang HAO
- Publication Type:Journal Article
- Keywords:
Carcinoma,squamous cell;
Mitogen-activated protein kinase kinases;
Tumor suppressor protein p53;
Cell line,tumor;
Resveratrol
- From:
Chinese Journal of Dermatology
2013;(4):248-252
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of resveratrol on the growth of an established A431 xenogratt 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.Significant differences were observed in the xenograft tumor volume (F =16.00,P ＜ 0.05) and weight (F =19.15,P ＜ 0.05) among the 6 groups.According to the tumor weight,the growth of tumor was inhibited by 45.57％,37.97％ and 15.51％ respectively in the high-,medium-and low-dose resveratrol groups.Increased apoptotic index was observed in the positive control group,high-,medium-and low-dose resveratrol groups compared with the negative control group and blank control group (36.79 ± 8.86,33.15 ± 6.00,18.09 ±3.92 and 10.53 ± 4.20 vs.3.87 ± 1.63 and 2.73 ± 1.61,F =93.26,P ＜ 0.05).Analysis of variance showed that the protein expressions of p-ERK,p53 and caspase 3 were all higher in the three resveratrol groups than in the negative control group and blank control group (F =6.65,6.78,11.56,respectively,all P ＜ 0.05).The protein expression of p53 was statistically correlated with p-ERK (r =0.68,P ＜ 0.05) and caspase 3 (r =0.56,P ＜0.05).Conclusions Resveratrol shows an inhibitory effect on the growth of human A431 skin squamous cell carcinoma xenografts in nude mice,likely by increasing p53 expression and inducing tumor cell apoptosis via the activation of MAPK/ERK pathway.
