摘要
In the present study, we investigated the antiproliferative effect and the underlying mechanism of three antidiabetic vanadium compounds, metavanadate, VO（acac）2 and VO（ma）2, in human prostate cancer cells （PC-3 and DU-145）. The results showed that vanadium compounds caused cell cycle arrest at G2/M phase evidenced by the elevation ofphosphorylated Cdc2 at tyr-15. Moreover, the results revealed that vanadium compounds induced reactive oxygen species （ROS） elevation in the two cell lines. The decreased level of Cdc25C could be rescued by the antioxidant, N-acetylcysteine, indicating that vanadium compounds-induced G2/M arrest was mediated by ROS. Additionally, the three vanadium compounds exerted more potent growth inhibitory effect on PC-3 cells which are PTEN-deficient and with higher level of basal ROS. It suggested that PTEN protein might serve as a biomarker for the selectivity of antitumor therapy using ROS-generating agents. Since the studied vanadium compounds have been shown the antidiabetic activities in the previous studies, there may be additional benefits in the potential application of vanadium compounds to suppress the growth of prostate cancer cells.
本研究以恶性程度不同的两种前列腺癌细胞PC-3和DU-145为模型,研究了具有降糖活性的钒化合物metavanadate、VO(acac)_2和VO(ma)_2的增殖抑制效应及机制。结果表明,在两种细胞中,三种钒化合物均可诱导细胞阻滞于G2/M期,表现在Cdc2的第15位酪氨酸的磷酸化水平升高。结果还显示,钒化合物能够引起ROS水平升高,且抗氧化剂N-乙酰半胱氨酸能恢复由于钒化合物诱导下降的Cdc25C蛋白水平,这说明活性氧在钒化合物引起的周期阻滞中起到调节作用。此外,研究表明钒化合物对PTEN缺失且ROS本底水平较高的PC-3的抑制作用强于对DU-145细胞,这提示PTEN可作为生物标记物而为患者抗肿瘤方案的选择提供依据。由于所研究的钒化合物已被证实具有抗糖尿病活性,因此其在抑制前列腺癌细胞的作用中可能具有独特的优势。
基金
National Natural Science Foundation of China(G rant No.21171011 and 21671009)
