Notch信号通路在胰岛素调节子宫内膜癌细胞生长及凋亡中的作用

发布时间：2018-03-31 17:56

本文选题：子宫内膜肿瘤　切入点：胰岛素　出处：《重庆医学》2017年29期

【摘要】：目的探讨抑制Notch信号传导对胰岛素诱导子宫内膜癌细胞增殖及相关凋亡蛋白表达水平的影响。方法将子宫内膜癌Ishikawa 3-H-12细胞行体外原代及传代培养,将培养好的细胞分为:对照组(加入磷酸盐缓冲液3mL)、胰岛素组(加入1×106 mol/L胰岛素单独刺激)及MW167组(应用不同剂量γ分泌酶抑制剂MW167预处理后再用胰岛素刺激),培养48h后应用噻唑蓝(MTT)比色法测定各组子宫内膜癌细胞生长抑制情况,应用蛋白质印迹法(Western blot)测定半胱氨酰天冬氨酸蛋白酶(Caspase)-3、Caspase-8及Notch1蛋白表达情况。结果胰岛素可促进子宫内膜癌细胞中Notch1蛋白表达,刺激48h后Notch1蛋白表达水平明显高于对照组(P0.05),MW167可抑制胰岛素诱导Notch1蛋白表达,且抑制作用具有浓度依赖性。不同组别子宫内膜癌细胞在培养24、48、72h后570nm处吸光度(A570)值存在明显差异(P0.05),其中胰岛素组各时间点A570值均高于对照组(P0.05),胰岛素促子宫内膜癌细胞增殖在48h时达到最高水平。MW167以浓度及时间依赖的方式抑制胰岛素促子宫内膜癌细胞增殖,在48h时20μmol/L MW167可持久抑制胰岛素促子宫内膜癌细胞的增殖。胰岛素组各时间点Caspase-3、Caspase-8蛋白表达水平低于对照组(P0.05),MW167以浓度及时间依赖的方式促进细胞Caspase-3、Caspase-8蛋白表达。结论 MW167可通过抑制Notch信号通路传导而抑制胰岛素促子宫内膜癌细胞增殖及促进相关凋亡蛋白表达,诱导子宫内膜癌细胞凋亡。
[Abstract]:Objective to investigate the effect of inhibition of Notch signal transduction on insulin-induced endometrial carcinoma cell proliferation and expression of apoptotic protein. Methods endometrial carcinoma Ishikawa 3-H-12 cells were cultured in vitro. The cultured cells were divided into three groups: control group (3 mL / L phosphate buffer), insulin group (1 脳 10 ~ 6 mol/L insulin alone) and MW167 group (pretreated with different doses of 纬 -secretase inhibitor MW167 before insulin stimulation). After 48 hours of culture, the growth inhibition of endometrial cancer cells in each group was determined by MTT assay. Western blotting was used to detect the expression of caspase-8 and Notch1 protein in cysteine aspartate protease. Results Insulin could promote the expression of Notch1 protein in endometrial carcinoma cells. After 48h stimulation, the expression of Notch1 protein was significantly higher than that of control group (P0.05 / MW167), which inhibited the expression of Notch1 protein induced by insulin. The inhibitory effect was concentration-dependent. There was a significant difference in the absorbance of A570 at 570nm in different groups of endometrial cancer cells cultured for 72 h, and the A570 value of insulin group was higher than that of control group at each time point. Insulin promoted endometrium. The proliferation of cancer cells reached the highest level at 48h. MW167 inhibited the proliferation of endometrial carcinoma cells induced by insulin in a dose-and time-dependent manner. At 48 h, 20 渭 mol/L MW167 could significantly inhibit the proliferation of endometrial carcinoma cells induced by insulin. The expression level of Caspase-3 Caspase-8 protein in insulin group was lower than that in control group (P 0.05). Conclusion the expression of Caspase-3 and Caspase-8 protein was enhanced in a dose-and time-dependent manner in insulin group. MW167 can inhibit the proliferation of endometrial carcinoma cells induced by insulin and promote the expression of related apoptotic proteins by inhibiting Notch signal transduction. Induction of apoptosis in endometrial cancer cells.
【作者单位】：广东省深圳市人民医院妇科;
【分类号】：R737.33

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