替拉扎明联合磷脂酰肌醇-3激酶抑制剂对人卵巢癌细胞的抑制作用  

Inhibitory effect of tirapazamine combined with phosphatidylinositol 3-kinase inhibitor LY294002 to ovarian cancer cells

作　　者：任源[1] 查晓[1] 张国楠[2] 

机构地区：[1]四川省肿瘤医院分子药理室,成都610041 [2]四川省肿瘤医院妇瘤科,成都610041

出　　处：《中华医学杂志》2007年第17期1204-1206,共3页National Medical Journal of China

基　　金：四川省科技厅重点科技项目(03SG022)

摘　　要：目的研究替拉扎明(TPZ)联合磷脂酰肌醇-3激酶抑制剂(LY294002)对人卵巢癌细胞株的体外抑制作用。方法乏氧及空气条件下,TPZ 单用及联合 LY294002在不同药物浓度下分别作用于人卵巢癌细胞株 H08910PM 和 OVCAR-3,用四甲基偶氮唑蓝(MTT)比色法评价其抑癌效果。结果在乏氧及空气条件下单独使用 TPZ 对 HO8910PM 的 IC_(50)分别为40.6 μmol/L 和53.0 μmol/L,对 OVCAR-3的 IC_(50)分别为65.9 μmol/L 和97.4 μmol/L;乏氧及空气条件下 TPZ 联用 LY294002,对HO8910PM 的 IC_(50)分别为22.7 μmol/L 和31.5 μmol/L,对 OVCAR-3的 IC_(50)分别为49.1 μmol/L 和51.0 μmol/L。结论 TPZ 对人卵巢癌细胞株有抑制作用,抑癌效果在乏氧条件下高于空气条件(P<0.01);LY294002对 TPZ 有协同作用,与 TPZ 单独用药相比,二者联用显著降低了 TPZ 对癌细胞的IC_(50)(P<0.01)。Objective To study the inhibitory effect of tirapazamine （TPZ） combined with LY294002 , an inhibitor of phosphatidylinositol 3-kinase （ PI3K ） , on the growth of human ovarian carcinoma ceils. Methods Human ovarian carcinoma ceils of the line HO8910PM were cultured and treated with tirapazamine alone and treated with TPZ of different concentrations combined with LY294002 of the concentration of 50 μmol/L respectively under aerobic and hypoxic conditions. And human ovarian carcinoma cells of the line OVCAR-3 were cultured and treated with YPZ alone and treated with TPZ of different concentrations combined with LY294002 of the concentration of 25 μmol/L respectively under aerobic and hypoxic conditions. MTr method was used to detect the surviving fractions of these carcinoma ceils, Results The IC50 values of TPZ on the HO8910PM ceils under hypoxic condition was 40.6 μmol/L, significantly lower than that under aerobic condition （53.0 μmol/L, P 〈0.01 ）. The ICso values of TPZ on the OVCAR-3 ceils under hypoxic condition was 65.9 μmol/L, significantly lower than that under aerobic condition （97.4 μmol/L, P 〈0.01 ）. The IC50 value of TPZ combined with LY294002 on the HP8910PM ceils under hypoxic condition was 22.7 μmol/L, significantly lower than that under aerobic condition （31.5 μmol/L, P 〈0.01 ）. The IC50 value of TPZ combined with LY294002 on the OVCAR-3 ceils under hypoxic condition was 49.1 μmol/L, not significantly different from that under aerobic condition （51.0 μmol/L, P 〉 0.05）. Conclusion TPZ inhibits the growth of human ovarian carcinoma ceils. The inhibitory effects of TPZ on the growth of human ovarian carcinoma cell of the lines HO8910PM and OVCAR-3 under hypoxic conditions are significantly higher than those under aerobic conditionl. LY294002 increases the inhibitory effect of TPZ on the ovarian cancer ceils, compared with TPZ treatment alone, TPZ combined with LY294002 decreases the IC50 of HO8910PM and OVCAR-3 ceils significantly.

关 键 词：1-磷脂酰肌醇3-激酶 细胞缺氧 卵巢肿瘤 抗肿瘤药 

分 类 号：R737.31[医药卫生—肿瘤]