干扰表皮生长因子受体磷酸化过程对乳腺癌的抑制效应

目的 探讨干扰表皮生长因子受体(EGFR)的磷酸化过程对裸鼠乳腺癌移植瘤生长的影响及其作用机制.方法 建立裸鼠乳腺癌移植瘤模型,成型后随机分为Ad5-hSulf1组、Ad5-EGFP组和对照组,干预治疗后,测量计算移植瘤生长率,采用免疫组化法检测各组裸鼠移植瘤hSulf-1、EGFR和p-EGFR阳性表达,采用Western blot法检测各组裸鼠移植瘤hSulf-1、EGFR和p-EGFR蛋白表达.结果 Ad5-hSulf1组裸鼠注射治疗后第14天、21天和28天的肿瘤生长率[(165.9±23.8)％,(172.6±25.9)％,(377.3±30.5)％]明显小于同期的对照组,差异均具有统计学意义(t=12.153,21.247,14.587;P =0.000).Ad5-hSulf1组裸鼠移植瘤p-EGFR阳性表达率(46.7％)和蛋白表达[(52.7±7.4)％]明显低于Ad5-EGFR组和对照组,差异均有统计学意义(x2=8.146,t=7.384,7.587;P =0.004、0.000、0.000).结论 使用hSulf1基因抑制乳腺癌细胞的EGFR磷酸化过程,可产生明显的肿瘤抑制效应,对寻求肿瘤基因治疗的一个很有潜力的靶点具有很好的借鉴参考意义.

Inhibitory effect of the phosphorylation of epidermal growth factor receptor on breast cancer

Objective To discuss the influence of epidermal growth factor receptor (EGFR) phosphorylation on the growth of breast cancer.Methods Nude mice model of breast cancer transplantation tumor was established.Mice were randomly divided into Ad5-hSulf1 group,Ad5-EGFP group and control group.The growth rate of transplanted tumor was measured after treatment.The positive expression of hSulf-1,EGFR and p-EGFR in the nude mice were detected by immunohistochemistry,hSulf-1,EGFR and p-EGFR protein expression in the nude mice of each group was detected by blotting Western method.Results The tumor growth rate of Ad5-hSulfl group at the,21 and 28 day after transplantation [(165.9 ± 23.8) ％,(172.6 ± 25.9) ％,(377.3 ± 30.5) ％] were significantly less than that of the control group,the difference were statistically significant(t =12.153,21.247,14.587,P =0.000).The positive expression rate (46.7％)and protein expression [(52.7 ± 7.4)％] of p-EGFR in Ad5-hSalf1 group was significantly lower than that in Ad5-EGFR group and control group.The difference were statistically significant (x2 =8.146,t =7.384,7.587,P =0.004,0.000,0.000).Conclusion To use hSulf-1 gene to inhibit the phosphorylation of EGFR in breast cancer cells can produce significant inhibitory effect on tumor.