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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 study the effects of epidermal growth factor (EGF) on the proliferation of estrogen receptor (ER) negative breast cancer cell lines in vitro and in nude mice and the effects of protein kinase C (PKC) inhibitor Go6976 on it. Methods: The effects of EGF and Go6976 on the cell cycle of ER-negative breast cancer cell lines were studied by flow cytometry. The growth of implanted tumors in nude mice model of breast cancer was observed continuously for 7 weeks. Results: Flow cytometry showed that the percentage of cells in G2 / M and S phase in EGF group increased compared with control group, the proliferation index (PI) reached 0.31, and EGF increased the proliferation of tumor cells. The cells in G0 / G1 phase of EGF + Go6976 group accounted for 91.54%, PI 0.09 (P <0.01), which showed that Go6976 could inhibit the proliferation of EGF. The growth of implanted tumors in nude mice showed that the tumor volume of EGF group increased most rapidly and that of Go6976 group was the slowest. In the tumor weight observation, the EGF group tumors increased about 78% (P <0.01) compared with the control group, indicating that EGF can promote ER-negative breast cancer cell line MDA-MB-435S growth in nude mice, while Go6976 + EGF group and EGF Compared with the control group, the weight of the implanted tumor decreased (P <0.01), indicating that Go6976 can inhibit the tumor growth promoting effect of EGF. CONCLUSIONS: EGF family growth signals have been shown to promote the proliferation of ER-negative breast cancer cells both in vitro and in nude mice in vivo. PKC, as an important participant in the EGF family signaling process, inhibits the activity of PKC and plays an inverse regulatory role in EGF signaling.