Sterol Regulatory Element-Binding Protein-1/Fatty Acid Synthase Involvement in Proliferation Inhibition and Apoptosis Promotion Induced by Progesterone in Endometrial Cancer
Sterol Regulatory Element-Binding Protein-1/Fatty Acid Synthase Involvement in Proliferation Inhibition and Apoptosis Promotion Induced by Progesterone in Endometrial Cancer
复制标题
甾醇调节元件结合蛋白-1/脂肪酸合酶参与孕酮诱导的子宫内膜癌增殖抑制和凋亡促进
DOI：
10.1097/igc.0000000000000004
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发表时间：
2013-11-01
影响因子：
4.8
通讯作者：
Jiang, Jie
中科院分区：
文献类型：
--
作者：
Qiu, Chunping;Dongol, Samina;Jiang, Jie
背景：子宫内膜癌（EC）病例数量迅速上升，生存率没有明显改善。孕酮受体的下调导致孕酮抗性，是目前治疗方面的主要问题。在此基础上，我们可以更多地关注由孕酮控制的下游信号通路。固醇调节元件结合蛋白-1/脂肪酸合成酶介导的脂质生物合成SREBP-1/FREB对EC细胞的生长和增殖至关重要，因此我们推测SREBP-1/FREB可能通过孕酮诱导的作用参与抑制EC细胞的增殖和促进其凋亡。使用细胞计数试剂盒-8分析醋酸甲地孕酮（MA; MA是孕酮衍生物，也称为17 α-乙酰氧基-6-甲基孕酮）处理后石川细胞的生长抑制率，并测定50%抑制浓度。通过使用Annexin V-FITC/碘化丙啶在不同时间间隔用50%抑制浓度的MA处理细胞来分析凋亡率。结果：MA处理的石川细胞生长受到明显抑制，并呈时间和浓度依赖性。实验组细胞凋亡率明显高于对照组（P < 0.01）。结论：Sterol Regulatory Element-binding Protein-1/FREBP-1/FREBP-1参与了MA对石川细胞的增殖抑制和促凋亡作用。
Background: The number of endometrial cancer (EC) cases is escalating rapidly, with no evident improvements in survival rates. The downregulation of progesterone receptor, resulting in progestin resistance, is presently a major problem regarding the therapeutic aspect. On the basis of this, we can focus more on the downstream signaling pathways that are controlled by progesterone. Lipid biosynthesis mediated by sterol regulatory element-binding protein-1/fatty acid synthase (SREBP-1/FASN) is of utmost importance to the growth and the proliferation of EC cells, so we hypothesize that SREBP-1/FASN might be involved in suppressing the proliferation and promoting apoptosis in EC cells through the effects induced by progesterone.Material and Methods: The Cell Counting Kit-8 was used to analyze the growth inhibition ratio of Ishikawa cells upon treatment with megestrol acetate (MA; MA is a progesterone derivative, also known as 17 alpha-acetoxy-6-dehydro-6-methylprogesterone) and to determine the 50% inhibitory concentration. Apoptosis ratio was analyzed by treatment of the cells with MA at 50% inhibitory concentration at different time intervals using Annexin V-FITC/propidium iodide. The protein and messenger RNA levels of SREBP-1 and FASN were compared between the experimental and control groups (MA-treated Ishikawa cells were considered to be the experimental group).Results: The experimental group showed obvious growth inhibition that was time and concentration dependent. The apoptosis ratio was also significantly higher in the experimental group compared with the control group (P < 0.01). The protein and messenger RNA levels of SREBP-1 and FASN were significantly reduced by MA too.Conclusions: Sterol regulatory element-binding protein-1/FASN is involved in the proliferation suppression and apoptosis promotion brought about by MA in Ishikawa cells.