Yang Feng-Qiang, Liu Min, Li Wei, Che Jian-Ping, Wang Guang-Chun, Zheng Jun-Hua
Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China.
Mol Med Rep. 2015 Feb;11(2):1085-92. doi: 10.3892/mmr.2014.2813. Epub 2014 Oct 29.
Previous studies have reported that hyperoside and quercetin in combination (QH; 1:1) inhibited the growth of human leukemia cells. The aim of the present study was to investigate the anti‑cancer effect of QH on prostate cancer cells. The results demonstrated that QH decreased the production of reactive oxygen species (ROS) and increased antioxidant capacity in PC3 cells at various concentrations (2.5‑60 µg/ml) with peak inhibition and augmentation changes of 3.22‑ and 3.00‑fold, respectively. Following treatment with QH for 48 and 72 h, the IC50-values on PC3 cells were 19.7 and 12.4 µg/ml, respectively. Western blot analysis revealed that QH induced apoptosis in human prostate cancer cells via activation of caspase‑3 and cleavage of poly(adenosine diphosphate ribose) polymerase. In addition, QH significantly inhibited the invasion and migration of PC3 cells as well as reduced the expression of numerous prostate tumor‑associated microRNAs (miRs), including miR‑21, compared to that of untreated human prostate cancer cells. QH was also found to enhance the expression of tumor suppressor programmed cell death protein 4, which was negatively regulated by miR‑21. Furthermore, induced overexpression of miR‑21 using pre‑miR‑21 oligonucleotides attenuated the beneficial effect of QH on prostate cancer cells. In conclusion, the results of the present study indicated that QH exerted an anti‑cancer effect on human prostate cancer cells, the mechanism of which proceeded, at least in part, via the inhibition of the miR‑21 signaling pathway.
先前的研究报道,金丝桃苷和槲皮素联合使用(QH;1:1)可抑制人白血病细胞的生长。本研究的目的是探讨QH对前列腺癌细胞的抗癌作用。结果表明,QH在不同浓度(2.5-60μg/ml)下可降低PC3细胞中活性氧(ROS)的产生并提高抗氧化能力,其抑制和增强作用的峰值变化分别为3.22倍和3.00倍。用QH处理48小时和72小时后,对PC3细胞的IC50值分别为19.7和12.4μg/ml。蛋白质印迹分析显示,QH通过激活半胱天冬酶-3和切割聚(二磷酸腺苷核糖)聚合酶诱导人前列腺癌细胞凋亡。此外,与未处理的人前列腺癌细胞相比,QH显著抑制PC3细胞的侵袭和迁移,并降低包括miR-21在内的多种前列腺肿瘤相关微小RNA(miR)的表达。还发现QH可增强肿瘤抑制因子程序性细胞死亡蛋白4的表达,该蛋白受miR-21负调控。此外,使用pre-miR-21寡核苷酸诱导miR-21过表达减弱了QH对前列腺癌细胞的有益作用。总之,本研究结果表明,QH对人前列腺癌细胞具有抗癌作用,其机制至少部分是通过抑制miR-21信号通路实现的。