Satari Atefeh, Amini Sayed Asadollah, Raeisi Elham, Lemoigne Yves, Heidarian Esfandiar
Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Adv Pharm Bull. 2019 Aug;9(3):462-469. doi: 10.15171/apb.2019.055. Epub 2019 Aug 1.
Prostate cancer is as far the most prevalent male cancer. Rutin (a glycoside from quercetin flavonoid) displays antioxidant activity leading to cell apoptosis. Combined effects of rutin with the widely used anti-cancer drug, 5-fluorouracil (5-FU), on prostate cancer cell line (PC3) was investigated herein. Different concentrations of combined 5-FU and rutin were applied to PC3 cells compared to separate treatment for 48 hours. Cell viability, as well p53 gene expression respectively were assessed by MTT assay and real-time quantitative polymerase chain reaction (qPCR). Changes of Bcl-2 signal protein and apoptosis were determined using western blot and flow cytometry procedures, respectively. Clonogenic assay was used to colony counts assessment. 50% inhibitory concentration (IC50) of separate cell treatment with either rutin and 5-FU respectively were 900 μM and 3Mm, while combination index (CI) of combined 5-FU /rutin application reached a level of synergistic effects (0.33). Combination of 5-FU/rutin enhanced apoptosis and p53 gene expression in PC3 cells. PC3 cell colony counts and Bcl-2 signaling protein were decreased by 5-FU/rutin combination. Synergistic effects of 5-FU/rutin combination on PC3 cells line enhanced apoptosis, p53 gene expression, and down-regulation of Bcl-2 protein, compared to control separate application. 5-FU/rutin combination does seem an interesting therapeutic pathway to be further investigated.
前列腺癌是目前最常见的男性癌症。芦丁（一种来自槲皮素类黄酮的糖苷）具有抗氧化活性，可导致细胞凋亡。本文研究了芦丁与广泛使用的抗癌药物5-氟尿嘧啶（5-FU）联合对前列腺癌细胞系（PC3）的影响。将不同浓度的5-FU和芦丁联合应用于PC3细胞，并与单独处理进行比较，处理48小时。分别通过MTT法和实时定量聚合酶链反应（qPCR）评估细胞活力以及p53基因表达。分别使用蛋白质印迹法和流式细胞术检测程序测定Bcl-2信号蛋白的变化和细胞凋亡情况。采用克隆形成试验评估集落计数。芦丁和5-FU单独处理细胞的50%抑制浓度（IC50）分别为900 μM和3 mM，而5-FU/芦丁联合应用的联合指数（CI）达到协同效应水平（0.33）。5-FU/芦丁联合应用可增强PC3细胞中的细胞凋亡和p53基因表达。5-FU/芦丁联合应用可降低PC3细胞集落计数和Bcl-2信号蛋白水平。与单独应用对照相比，5-FU/芦丁联合应用对PC3细胞系的协同效应增强了细胞凋亡、p53基因表达，并下调了Bcl-2蛋白。5-FU/芦丁联合应用似乎是一条值得进一步研究的有趣治疗途径。
