Guttiferone K抑制静止期前列腺癌细胞重新激活的作用研究

Effect of Guttiferone K on Inhibiting Reactivation of Quiescent Prostate Cancer Cells

目的:观察从云南藤黄(Garcinia yunnanensis)中提取分离得到的PPAPs(Polycyclic Polyprenylated Acylphloroglucinol)类化合物Guttiferone K(GUTK)对人静止期前列腺癌LNCa P细胞重新激活的影响。方法:处于对数生长期的人前列腺癌LNCa P细胞去除血清培养7d诱导其进入静止期,通过再次加入血清培养使其重新激活进入细胞周期,同时给予GUTK进行干预。用免疫细胞化学的方法检测Ki-67蛋白表达的变化;利用PI染色的流式分析法和Ed U Incorporation法检测GUTK对细胞周期分布的影响;利用Western Blotting法检测Cyclin D1/3、CDK4/6和E2F1蛋白表达水平的变化。结果:GUTK呈剂量依赖性地抑制静止期LNCa P细胞的再次增殖并阻止静止期LNCa P细胞重新进入S期;GUTK在静止期LNCa P细胞激活的早期明显下调了Cyclin D1/3、CDK4/6和E2F1蛋白的表达水平。结论:从云南藤黄中提取分离得到的化合物GUTK能够抑制人静止期前列腺癌LNCa P细胞的重新激活,具有潜在的延缓前列腺癌病情发展和预防复发的作用。

Objective： To investigate the effect of Guttiferone K（ GUTK）,a polycyclic polyprenylated acylphloroglucinol（ PPAPs）compound isolated from Garcinia yunnanensis,on inhibiting reactivation of quiescent prostate cancer LNCa P cells. Methods： LNCa P cells were induced into a quiescent stage by seven days of serum withdrawal and stimulated cell cycle re-entry with or without GUTK by serum restoration. Ki-67 protein expression level was detected by Immunocytochemistry. Flow cytometry of Propidium iodide（ PI） staining and Ed U Incorporation assay were used to analyze cell cycle phase distribution. Protein levels of Cyclin D1 /3、CDK4 /6 and E2F1 were detected by Western blotting. Results： GUTK dose-dependently blocked the re-proliferation and S phase reentry of quiescent LNCa P cells. GUTK decreased the Cyclin D1 /3、CDK4 /6 and E2F1 protein levels during quiescent LNCa P cell cycle re-entry. Conclusion： GUTK,a compound isolated from Garcinia yunnanensis,has the potential to inhibit cancer progression and prevent cancer recurrence by suppressing cell cycle re-entry of quiescent prostate cancer LNCa P cells.