Abstract: 【Abstract】〓Objective〓To investigate the in vitro and in vivo effects of quercetin and its derivative (quercetin-7-sulphate) on human bladder cancer cells by using the BIU-87 cell line and nude mice. Methods〓The BIU-87 cells were exposed to different concentrations of quercetin and sodium quercetin-7-sulphate (SQMS). Cell proliferation and the half maximal inhibitory concentration (IC50) values were determined by MTT assay, and cell cycle was evaluated by flow cytometry. Tumor masses were weighed and tumor inhibition rate were calculated in tumor bearing mice treated with quercetin and SQMS at low, medium and high concentration respectively. Tumor tissue specimen were processed for histological analysis. The expression levels of Ki-67, Cyclin D1 and Cyclin B1 were evaluated by using immunohistochemistry..Results〓Both quercetin and SQMS showed inhibitory effects on proliferation in BIU-87 cells in a dose-dependent manner,.with no statistically significant difference observed between quercetin and SQMS groups of the same concentration.(P>0.05). Quecertin significantly arrested the growth of BIU-87 cells at G2/M phase,.while SQMS mainly arrested them at G0/G1 phase..The in vivo tumor inhibition capacity of quecertin was comparable to that of SQMS administrated at medium concentration(P>0.05)..Quecertin more potently down-regulated the expression of Cyclin B1.(P<0.05).while SQMS more potently down-regulated the expression of CyclinD1 (P<0.01). But there was no significant effect on Ki-67 expression (P>0.05). Conclusion〓Both quercetin and SQMS showed a significant anti-tumor effect not only on the BIU-87 bladder cancer cell line but also on bladder carcinoma in nude mice. Medium concentration SQMS showed similar in vivo inhibitory effect to that of quercetin. Quecertin significantly arrested bladder cancer cells at G2/M phase probably by down-regulating the expression of Cyclin B1,.while SQMS significantly arrested the cancer cells at G0/G1 phase,.at least partly,.by down-regulating the expression of CyclinD1.

Key words: Quercetin, Derivatives bladder carcinoma, Cell cycle

摘要： 【摘要】 目的 通过细胞试验及裸鼠移植瘤实验,研究槲皮素及其7-OH衍生物对人膀胱癌BIU-87细胞的增殖抑制作用及细胞周期的影响。方法〓体外实验:培养BIU-87细胞,分别加入槲皮素(QUE)及槲皮素单硫酸酯钠盐(SQMS),MTT实验测定并计算生长抑制率及半数抑制浓度IC50;流式细胞仪检测细胞周期。体内实验:观察不同剂量SQNS及槲皮素对BIU-87细胞裸鼠移植瘤生长的抑制作用;瘤体组织切片行HE染色和免疫组化染色检测Ki-67,CyclingB1,CyclingD1蛋白表达情况。结果〓槲皮素及SQMS体外均能抑制BIU-87细胞的增殖,相同浓度两药物间对比差异无统计学意义(P>0.05)。槲皮素使BIU-87细胞周期明显阻滞于G2/M期,而SQMS则主要阻滞于G0/G1期。在体内实验中,中等剂量的SQMS组抑瘤率与槲皮素组相近(P>0.05),CyclingD1表达比槲皮素组下调更明显(P<0.01),而槲皮素组CyclingB1表达比中剂量SQMS组下调更明显(P<0.05)。两组Ki-67表达无显著性差异(P>0.05)。结论〓槲皮素及其衍生物SQMS对膀胱癌细胞BIU-87有抑制增殖作用;中剂量的SQMS对成瘤生长的抑制作用与槲皮素作用相近;槲皮素对人膀胱癌细胞增殖抑制作用可能是通过下调CyclingB1的表达,阻滞细胞周期于G2/M期,而SQMS则可能是通过下调CyclingD1的表达,阻滞细胞周期于G0/G1期。

关键词: 槲皮素衍生物, 膀胱癌, 细胞周期