上海交通大学学报（医学版）

›› 2010, Vol. 30 ›› Issue (5): 527-.

• 论著（基础研究） • 上一篇    下一篇

β-羟基异戊酰紫草素对前列腺癌细胞株的生长抑制作用及机制研究

刘 昕1, 牛 昕1, 周 文2, 易 静1   

  1. 上海交通大学 1.基础医学院细胞生物学教研室, 2.药学院, 上海 200025
  • 出版日期:2010-05-25 发布日期:2010-05-28
  • 通讯作者: 易 静, 电子信箱: yijing@shsmu.edu.cn。
  • 作者简介:刘 昕（1986—）, 女, 硕士生；电子信箱: liuxin_juju@yahoo.com.cn。
  • 基金资助:

    上海市科委基础研究重点项目（08JC1413800）

Growth inhibitory effect of β-hydroxyisovalerylshikonin on prostate cancer cells and related mechanism

LIU Xin1, NIU Xin1, ZHOU Wen2, YI Jing1   

  1. 1.Department of Cell Biology, Basic Medical College, 2.School of Pharmacy, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2010-05-25 Published:2010-05-28
  • Supported by:

    Shanghai Science and Technology Committee Foundation, 08JC1413800

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摘要：

目的 研究β-羟基异戊酰紫草素（β-HIVS）对激素非依赖性前列腺癌细胞株PC-3的体外生长抑制作用及其可能机制。方法 采用MTT法检测β-HIVS对PC-3和人皮肤成纤维细胞株HSF的细胞生长抑制率；荧光素酶报告基因法检测给药后细胞中低氧诱导因子-1（HIF-1）和核因子κB（NF-κB）的转录活性；RT-PCR检测HIF-1下游靶基因血管内皮生长因子（VEGF）的表达；Western blotting检测β-HIVS作用后HIF-1α蛋白的表达水平。结果 β-HIVS对PC-3的细胞生长具有显著抑制作用（P<0.05），而对HSF的细胞生长无明显影响（P>0.05）。给药后PC-3细胞中NF-κB转录活性无明显变化（P>0.05）；而HIF-1转录活性受抑（P<0.05），其下游靶基因VEGF表达下调，且细胞中HIF-1α蛋白累积减少。结论 β-HIVS对PC-3的细胞生长具有抑制作用，其机制可能与β-HIVS减少低氧条件下PC-3中HIF-1α蛋白水平，抑制其转录活性，使下游促细胞生长靶基因VEGF表达下调有关。

关键词: β-羟基异戊酰紫草素, 前列腺癌, 低氧诱导因子-1, 血管内皮生长因子

Abstract:

Objective To investigate the growth inhibitory effects of β-hydroxyisovalerylshikonin (β-HIVS) on hormone-independent prostate cancer cell line PC-3, and explore the related mechanism. Methods The inhibition rates of β-HIVS on PC-3 cells and normal human skin fibroblasts (HSF) were determined by MTT method. Luciferase reporter assay was adopted to examine the transcriptional activity of hypoxia-inducible factor-1 (HIF-1) and nuclear factor-kappa B (NF-κB). The expression of vascular endothelial growth factor (VEGF), the target gene of HIF-1, was detected by RT-PCR. The expression of HIF-1α protein in PC-3 cells treated by β-HIVS was detected by Western blotting. Results β-HIVS significantly inhibited the growth of PC-3 cells (P<0.05), while had no significant effect on HSF cells (P>0.05). There was no significant change in transcriptional activity of NF-κB in PC-3 cells after drug treatment (P>0.05). β-HIVS inhibited the transcriptional activity of HIF-1 and decreased the expression of VEGF. The protein level of HIF-1α in PC-3 cells was reduced by β-HIVS. Conclusion β-HIVS inhibits the growth of PC-3 cells by decreasing the level of HIF-1α protein in PC-3 cells under hypoxia condition, thus attenuating the transcriptional activity of HIF-1α and decreasing the expression of VEGF.

Key words: β-hydroxyisovalerylshikonin, prostate cancer, hypoxia-inducible factor-1, vascular endothelial growth factor