AGl024对子宫内膜癌细胞系增殖与凋亡的影响.docVIP

 n  AGl024 对子宫内膜癌细胞系增殖与凋亡的 影响# 王春芳，李小平，魏丽惠** 5 10 15 20 （北京大学人民医院妇产科，北京 100044） 摘要：目的 探讨胰岛素样生长因子 I 型受体(IGF-IR)酪氨酸激酶阻断剂 AGl024 对人子宫 内膜癌细胞的增殖抑制作用和凋亡诱导作用。方法 采用 MTS、流式细胞术和 western blot 等方法检测在不同浓度的 AGl024 作用下，人子宫内膜癌细胞系 RL95-2 和 IR- A 过表达的 细胞系 RL95-2-IR-A 的生物学特性和信号传导通路的改变。结果 MTS 检测显示，AGl024 剂量依赖性地抑制子宫内膜癌细胞的增殖，与 RL95-2-IR-A 相比，AGl024 对 RL95-2 的抑 制增殖作用更显著。流式细胞术提示，显 AGl024 对子宫内膜癌细胞有显著的抗增殖作用和 凋亡诱导作用。western blot 结果显示， AGl024 可明显降低 RL95-2 和 RL95-2-IR-A 细胞中 磷酸化 ERK 的表达，而总的 ERK 量无明显变化。结论 AGl024 可以阻断 IGF-IR，从而阻 断其下游的信号传导途径，抑制子宫内膜癌细胞的增殖，诱导凋亡。 关键词：子宫内膜癌；细胞凋亡；IGF-IR；胰岛素受体亚型；酶抑制剂 The effect of AGl024 to proliferation and apoptosis of endometrial carcinoma Wang Chunfang, Li Xiaoping, Wei Lihui (Department of Gynecology, Peking University People’s Hospital, Beijing 100044) Abstract: Objective AGl024 is a tyrosine kinase inhibitor of the insulin-like growth factor type I receptor (IGF-IR).The purpose of this study is to investigate the effect of AG1024 on cell proliferation inhibition and apoptosis induction of human endometrial cancer. Methods treated with AGl024 on varied concentrations, the endometrial carcinoma cell line RL95-2 and 25 30 RL95-2-IR-A was observed for the biological characteristics and the signal pathway changes by MTS, Flow cytometry and western blot. Results MTS testing showed that AGl024 inhibited the proliferation of endometrial cancer dose-dependently. The inhibition proliferation effect of AGl024 on RL95-2 is more pronounced than that in RL95-2-IR-A. Flow cytometry shows that AGl024 have a significant antiproliferative effect and apoptosis induction to endometrial cancer. According to western blot results, AGl024 can significantly reducethe expression of phosphorylated ERK,while total ERK remained unchanged in the RL95-2 and RL95-2-IR-A cells. Conclusions AGl024 can block IGF-IR, thereby blocking its downstream signal transduction pathway and inhibit proliferation and induce apoptosis on endometrial cancer cells. Key words: endometrial cancer; apoptos