Go6976阻断EGF的促ER阴性乳腺癌细胞增殖作用

Go6976 block EGF-promoted proliferation in estrogen-negative breast cancer cells

目的:研究表皮生长因子(EGF)在体外和裸鼠模型体内促进雌激素受体(ER)阴性乳腺癌细胞株增殖作用,以及应用蛋白激酶C(PKC)抑制剂Go6976对该作用的影响。方法:以流式细胞技术研究EGF和Go6976对ER阴性乳腺癌细胞株细胞周期的影响,连续观察二者干预下的裸鼠乳腺癌模型的种植瘤生长情况7周。结果:流式细胞检测显示EGF组与对照组相比G2/M和S期细胞百分比增加,增殖指数(PI)达到0.31,EGF有促进肿瘤细胞增殖作用,EGF+Go6976组G0/G1期细胞占91.54%,PI为0.09(P<0.01),显示Go6976有抑制EGF的促增殖作用。对裸鼠种植瘤的生长观测显示EGF组肿瘤体积增长最快,而Go6976组肿瘤体积增长最慢。在肿瘤重量观察中,EGF组肿瘤较对照组增加约78%(P<0.01),显示EGF可以促进ER阴性乳腺癌细胞株MDA-MB-435S在裸鼠体内生长,而Go6976+EGF组与EGF组比较,种植瘤重量减少(P<0.01),显示Go6976可以抑制EGF的促肿瘤增殖作用。结论:EGF家族的生长信号无论在体外试验还是在裸鼠模型体内实验中都显示有促进ER阴性乳腺癌细胞的增殖的作用。PKC作为EGF家族信号传递过程的重要参与者,抑制其活性可以对EGF信号起到反向调节作用。

Objective： To investigate the function of epidermal growth factor （EGF）-promoted proliferation in estrogen-negative breast cancer cells in vitro and in nude mice model and the influence on that function from Go6976, a protein kinase C （PKC） inhibitor. Methods： The influence of EGF and Go6976 on cell-cycle was assayed by Flow cytometry （FCM）. The volume and the weight of implanted tumor in nude mice had been observed in seven weeks. Results： The data by FCM shew that the percentage of cells in phase GJM and S in group EGF was higher than that in group normal saline （NS） and the percentage of cells in phase G0/G1 in group EGF adding Go6976 was 91.54%. The proliferation index （PI） in group EGF was 0.31 （P = 0.01 ,compared with PI in group NS） and that in group EGF adding Go6976 was 0.09 （P 〈 0.01 ,compared with PI in group EGF ）. The tumor volume in group EGF grew faster than that in other three groups. The weight of tumor in group EGF increased about 78% than that in group NS （P 〈 0.01）. Conclusion： The signal from EGF family can promote proliferation in ER-negative breast cancer cells both in vitro and in nude mice body. The PKC play an important role in procedure of EGF signal transmission. The inhibitor of PKC, Go6976, can down-regulate the signal from EGF family.