2-甲氧雌二醇与槲皮素体外联合抗前列腺癌的作用  

Effect of 2-methoxyestradiol combined with quercetin on prostate cancer in vitro

作　　者：宋黎明[1] 王国栋[2] 王慧萍 邢念增[1] 

机构地区：[1]首都医科大学附属北京朝阳医院泌尿外科,100020 [2]北京电力医院泌尿外科 [3]国家卫生计生委科学技术研究所免疫药理室

出　　处：《中华医学杂志》2016年第2期95-99,共5页National Medical Journal of China

基　　金：北京市自然科学基金（7122075）

摘　　要：目的观察2-甲氧雌二醇（2-Methoxyestradiol，2-ME）和槲皮素（quercetin，Que）联合应用对人前列腺癌细胞系LNCaP和PC-3生长的作用，评价Que和2-ME联合用药的体外抗前列腺癌效果并筛选有协同作用的配伍组合。方法用不同浓度Que（0、3．125、6．25、12．5、25、50、100、200μmol／L）和2-ME（0、0．3125、0．625、1．25、2．5、5、10μmol／L）分别处理LNCaP和PC-3细胞，锥虫蓝法计数并计算48h癌细胞生长抑制率和半抑制浓度（IC50）。根据量效曲线与IC50值，分别选择两种药物的适宜浓度按照析因设计组成不同的联用配伍组合。应用不同药物配伍组分别处理LNCaP和PC-3细胞48h，测定细胞生长抑制率，并计算两种药物16个配伍组的联用指数（cI），以评价药物的体外联合抗前列腺癌效果。结果随单用Que或2-ME的浓度增加，其对LNCaP或PC-3细胞的生长抑制率增加。槲皮素和2-ME的IC50值分别为23．29μmol／L和1．89μmol／L（针对LNCaP细胞）；22．12μmol／L和1．74μmol／L（PC-3细胞）。选择Que（5、10、20、40μmoL／L）和2-ME（0．5、1、3、5μmol／L）组成16个配伍组作用于癌细胞48h后，低剂量槲皮素（5和10μmol／L）联合高剂量2-ME（3和5μmol／L）对LNCaP细胞生长表现出协同抑制作用；而对PC-3细胞，除了槲皮素10μmol/L＋2-ME 3μmol／L配伍组外，高剂量的槲皮素（20和40μmol／L）联合高剂量的2-ME（3和5μmol／L）也表现出协同作用。结论Que和2-ME对人前列腺癌细胞系LNCaP和PC-3的生长均具有抑制作用，并剂量相关性，两药合适剂量的配伍组合对前列腺癌细胞的生长抑制具有协同作用。Objective To detect the effects of quercetin （Que） combined with 2-methoxyestradiol （2-ME） on the proliferation of androgen-dependent LNCaP human prostate cancer cells line and androgen-independent PC-3 human prostate cancer cells line, and to evaluate the antitumor effects of different combos of the two drugs. Methods After LNCaP and PC-3 cells were treated with different concentration of quercetin （0,3. 125,6. 25,12. 5,25,50,100,200 μmol/L） or 2-ME （ 0,0. 312 5,0. 625,1.25,2. 5,5,10 μmol/L） for 48 h, the inhibitory rates of cell growth were tested using trypan blue staining method respectively. Then the concentration-effect curves were drawn and ICs0 values were calculated. According to the fitted dose-effect curves and ICs0 values, appropriate concentrations of quercetin and 2-ME were selected to compose 16 different combos. Then cells were treated with different combos of Que and 2-ME for 48 h, and then the growth inhibitory rates of cell growth were detected. According to the equation and medianeffect principle, the CI values of 16 different combos of Que and 2-ME were calculated to evaluate their antitumor effects. Results The inhibition rate of LNCaP or PC-3 cell growth treated with varying doses of quercetin or 2-ME alone showed a dose-dependent increase respectively. The IC50 values of quercetin and 2- ME were 23.29 μmol/L and 1.89 μmol/L for LNCaP cells; and 22. 12 μmol/L and 1.74 μmol/L for PC-3 cells respectively. After treated with 16 combos of Que （5, 10, 20, 40μmol/L） and 2-ME （0. 5, 1, 3, 5μmol/L） for48 h, for LNCaP cells, lower dose of Que （5 and 10μmol/L） with higher dose of 2-ME （5 and 5 μmol/L） showed synergistic activity, whereas for PC-3 cells, besides the above combination of Que 10 μmol/L and 2-ME 3 μmol/L, higher dose of quercetin （20 and 40 μmol/L） with higher dose of 2-ME （3 and 5 μmol/L） also showed synergistic activity. Conclusions Both quercetin and 2-methoxyestradiol could inhibit the growth of LNCaP and PC-3 human prostate cance

关 键 词：前列腺癌 2-甲氧雌二醇 槲皮素 协同作用 

分 类 号：R737.25[医药卫生—肿瘤]