摘要
目的:研究Herceptin下调乳腺癌细胞HER2表达对PI3K/Akt通路相关蛋白表达的影响,探讨该通路在Herceptin抗肿瘤效应中的作用。方法:Herceptin处理HER2过表达的乳腺癌细胞株SKBR-3,免疫细胞化学检测HER2、p21Cip1和p27Kip1的表达,Westernblot检测p-Akt和Bad的表达。结果:Herceptin处理组细胞HER2阳性表达率(37.4%)显著低于对照组(78.3%)(P<0.01)。Herceptin处理组与对照组比较,p-Akt蛋白含量降低53.5%(P<0.01),Bad蛋白含量升高0.83倍(P<0.01)。Herceptin处理组细胞p21Cip1和p27Kip1阳性表达率(分别为67%和56.1%)显著高于对照组(分别为19%和21.4%)(P<0.01)。结论:Herceptin下调HER2表达后,通过下调p-Akt表达而上调其下游Bad、p21Cip1和p27Kip1的表达,从而抑制肿瘤细胞增殖,促进肿瘤细胞凋亡。
Objective： To evaluate the influence of downregulated HER2 expression by Herceptin of breast cancer cells on the related protein expression via PI3K/Akt pathway, and to investigate the action of this pathway in the anti-tumor effect of Herceptin. Methods： The HER2 overexpressed breast cancer cell line SKBR-3 was treated with Herceptin, the expressions of HER2, p21^Cipl and p27^Kipl were detected by immunocytochemistry, and the expressions of p-Akt and Bad were detected by Western blot. Results： The rate of HER2 positive cells of Herceptin treated group（37.4%） compared to the untreated group（78.3%） decreased significantly （P〈0.01）. Compared to the untreated group, the amount of p-kt protein of Herceptin treated group decreased significantly to 53.5% （P〈0.01）, the amount of Bad protein of Herceptin treated group increased significantly by 0.83 fold（P〈0.01）. The rates of p21^Cipl and p27^Kipl positive cells of Herceptin treated group （67% and 56.1% respectively） compared to the untreated group （19% and 21.4% respectively） increased significantly （P〈0.01）. Conclusion： Herceptin can downregulate HER2 expression, to downregulate p-Akt expression and then to upregulate the expression of its downstream protein Bad, p21^Cipl and p27^Kipl, thus to inhibit the proliferation and promote the apoptosis of tumor cells.
出处
《温州医学院学报》
CAS
2008年第3期200-202,共3页
Journal of Wenzhou Medical College
基金
浙江省教育厅科研基金资助项目(20020469)
温州市科技局科研基金资助项目(S2002A122)
