| 颜廷芒,董 凯,周文豪,刘海涛,荆翌峰.维生素K3通过调控Ras信号通路抑制前列腺癌细胞增殖[J].,2018,(21):4001-4006 |
| 维生素K3通过调控Ras信号通路抑制前列腺癌细胞增殖 |
| Effect of Vitamin K3 on Proliferation of Prostate Cancer Cells by the Regulation of Ras Signal Pathway |
| 投稿时间：2018-04-28 修订日期：2018-05-23 |
| DOI：10.13241/j.cnki.pmb.2018.21.001 |
| 中文关键词: 维生素K3 Siah2 Ras/Raf/MEK/ERK信号通路 前列腺癌 |
| 英文关键词: Vitamin K3 Siah2 Ras/Raf/MEK/ERK signal pathway Prostate cancer |
| 基金项目:国家自然科学基金项目（81402091） |
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| 中文摘要: |
| 摘要 目的：研究维生素K3对前列腺癌细胞增殖的影响及其机制。方法：CCK-8检测维生素K3对前列腺癌细胞系增殖的影响；应用siRNA干扰Siah2表达之后，CCK-8检测维生素K3对前列腺癌细胞系增殖的影响；Western Blot检测维生素K3对前列腺癌细胞Siah2和Spry2表达的影响；免疫共沉淀技术检测维生K3对Siah2介导的Spry2泛素化水平的影响；Western Blot检测维生素K3对Ras信号通路中pERK表达的影响；构建裸鼠皮下前列腺癌模型，研究维生素K3对肿瘤生长的影响。结果：维生素K3抑制前列腺癌细胞系增殖，并且维生素K3浓度越高，对细胞抑制增殖作用越明显。前列腺癌细胞中干扰Siah2表达后，10 μM维生素K3对细胞增殖无明显抑制作用即维生素K3对前列腺癌细胞增殖抑制作用依赖Siah2。10 μM维生素K3能减弱Siah2对Spry2的泛素化水平使Spry 2表达升高。维生素K3能使前列腺癌细胞中Ras信号通路中的pERK蛋白表达降低。动物实验显示维生素K3治疗12天后，对照组和维生素K3组间肿瘤体积大小具有统计学差异，说明维生素K3能够有效地抑制裸鼠皮下前列腺癌生长。结论：维生素K3通过抑制Siah2泛素连接酶活性，介导其底物Spry2表达升高，进而抑制Ras/Raf/MEK/ERK信号通路起到抑制前列腺细胞增殖作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of vitamin K3 on proliferation of prostate cancer cells and its mechanism. Methods: CCK-8 was used to detect the effects of vitamin K3 on the proliferation of prostate cancer cells; CCK-8 were used to detect the effects of vitamin K3 on the proliferation of prostate cancer cells after treating with siSiah2; Western Blot was used to detect the effects of vitamin K3 on the expression of Siah2 and Spry2; Immunoprecipitation was performed to detect the effect of vitamin K3 on the ubiquitination of Spry2. Western Blot was used to detect the effects of vitamin K3 on the expression of pERK in Ras signal pathway. Constructing nude subcutaneous prostate cancer model to investigate the effects of vitamin K3 on the growth of the tumors. Results: Vitamin K3 can inhibit the proliferation of prostate cancer cells and the higher the concentration of vitamin K3, the more obvious the inhibition effect on cell proliferation. There were no inhibition effects of vitamin K3 on cell proliferation after treating with siSiah2, which means the inhibiting effects were Siah2 dependent. 10 μM Vitamin K3 increased the protein level of Siah2 and its substrate-Spry2 through decreasing its ubiquitination level of Spry2. Vitamin K3 decreased the pERK expression in Ras signal pathway. Animal experiments showed that after 12 days of vitamin K3 treatment, there was a statistical difference in tumor volume between control and vitamin K3 group, indicating that vi- tamin K3 can effectively inhibit the growth of subcutaneous prostate cancer in nude mice. Conclusion: Vitamin K3 inhibits the prolif- eration of prostate cancer cells dependent on Siah2 by down regulating Ras/Raf/MEK/ERK signal pathway. |
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