Zhao Jing, Zhang Li-Tao, Bai Yun, Wang Ze-Yang, Zhang Xue-Mei, Ma Chun-Ling
Department of Oncology, Hebei General Hospital, Shijiazhuang 050051, China.
Department of Emergency, Hebei General Hospital, Shijiazhuang 050051, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2019 Jul;50(4):546-550.
To investigate the expression of stearoyl-CoA desaturase-1 (SCD1) in breast cancer cell lines. To analyze the effect of inhibiting SCD1 activity on the proliferation and cell cycle of MCF-7 breast cancer cell and its mechanism.
The expression of SCD1 protein were detected by Western blot techniques in breast cancer cell lines and humanskin fibroblasts.Cell viability of MCF-7 cells treated with MF-438 was measured using MTS assay and IC value was calculated.The distribution of cell cycle was determined by PI staining using flow cytometry.The expression of Cyclin D1 was detected by Western blot. The expression of Akt, pAkt, pAMPK and pACC were also detected by Western blot.
The expression level of SCD1 in MCF-7 and MDA-MB-231 cells was significantly higher than that in HSF cells ( < 0.05).MF-438 showed a significant dose-dependent proliferation inhibition effect on MCF-7 cells cultured in low serum at a concentration ranging from 100 nmol/L to 100 μmol/L with an IC value of (3.9±0.45) μmol/L. After intervention of 5 μmol/L MF-438 in MCF-7 cells, the proportion of cells in S phase and G/M phase was significantly decreased ( < 0.01), the proportion of cells in G/G phase increased ( < 0.01), and the expression of Cyclin D1 was significantly decreased ( < 0.05); Meanwhile, the expression of pAkt and pAkt/Akt value were significantly decreased ( < 0.05) and the expression of pAMPK and pACC levels were significantly increased ( < 0.05).
SCD1 plays an important role in the occurrence and development of breast cancer. Inhibition of SCD1 activity can inhibit cell cycle progression and impair cell proliferation by down-regulating the Akt pathway and activating the AMPK pathway. Further research on SCD1 is expected to provide a new target for molecular targeted therapy of breast cancer.
研究硬脂酰辅酶A去饱和酶-1（SCD1）在乳腺癌细胞系中的表达情况。分析抑制SCD1活性对MCF-7乳腺癌细胞增殖及细胞周期的影响及其机制。
采用蛋白质免疫印迹技术检测乳腺癌细胞系及人皮肤成纤维细胞中SCD1蛋白的表达。用MTS法检测MF-438处理后MCF-7细胞的活力并计算IC值。采用流式细胞术PI染色法测定细胞周期分布。通过蛋白质免疫印迹法检测细胞周期蛋白D1（Cyclin D1）的表达。同时采用蛋白质免疫印迹法检测Akt、磷酸化Akt（pAkt）、磷酸化腺苷酸活化蛋白激酶（pAMPK）和磷酸化乙酰辅酶A羧化酶（pACC）的表达。
MCF-7和MDA-MB-231细胞中SCD1的表达水平显著高于人皮肤成纤维细胞（HSF细胞）（P<0.05）。MF-438在100 nmol/L至100 μmol/L浓度范围内对低血清培养的MCF-7细胞具有显著的剂量依赖性增殖抑制作用，IC值为（3.9±0.45）μmol/L。5 μmol/L MF-438干预MCF-7细胞后，S期和G/M期细胞比例显著降低（P<0.01），G0/G1期细胞比例增加（P<0.01），Cyclin D1表达显著降低（P<0.05）；同时，pAkt及pAkt/Akt值显著降低（P<0.05），pAMPK和pACC水平显著升高（P<0.05）。
SCD1在乳腺癌的发生发展中起重要作用。抑制SCD1活性可通过下调Akt信号通路和激活AMPK信号通路来抑制细胞周期进程并损害细胞增殖。对SCD1的进一步研究有望为乳腺癌的分子靶向治疗提供新靶点。
