双氢青蒿素对卵巢上皮癌细胞黏附、迁移和侵袭能力的影响  

Effects of dihydroartiminisin on the adhesion, migration, and invasion of epithelial ovarian cancer cells

作　　者：谭先杰[1] 郎景和[1] Jean Plouet 吴鸣[1] 沈铿[1] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院妇产科,100730 [2]法国国立健康医学研究院巴黎血液血管研究所

出　　处：《中华医学杂志》2008年第37期2642-2646,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目（30100199）;北京科技新星计划基金资助项目（2003A25）

摘　　要：目的观察双氢青蒿素对体外培养的卵巢上皮癌细胞黏附、迁移和侵袭能力的影响，并探讨相关的分子作用机制。方法以不用药物处理的SKOV3和OVCAR3卵巢上皮癌细胞为对照组，利用基质胶贴壁黏附法检测双氢青蒿素（研究组）对癌细胞体外黏附能力的影响，用跨膜小室模型检测双氢青蒿素对癌细胞迁移和侵袭能力的影响。用Western印迹和RT—PCR法分别检测双氢青蒿素对癌细胞聚焦黏附激酶（FAK）磷酸化的影响以及对基质金属蛋白酶（MMP）及其组织抑制因子（TIMP）表达的影响。结果（1）与对照组相比，双氢青蒿素使SKOV3和OVCAR3细胞的体外黏附能力分别降低76．1％和57．9％（P〈0．05），迁移能力降低59．3％和69．7％（P〈0．05）。（2）SKOV3和OVCAR3细胞的侵袭能力弱，双氢青蒿素对其侵袭能力无明确抑制作用。（3）与对照组比较，双氢青蒿素分别使SKOV3和OVCAR3细胞FAK蛋白磷酸化水平降低42．9％和44．8％（P〈0．05）。（4）SKOV3和OVCAR3细胞中未检测到MMP9的表达，双氢青蒿素能诱导TIMP1的表达，对MMP2和TIMP2的表达无影响。结论双氢青蒿素对卵巢上皮癌细胞侵袭能力的影响不明显，但能抑制其黏附和迁移能力，后两者可能与药物抑制癌细胞FAK的磷酸化水平有关。Objective To investigate the effects of dihydroartiminisin （DHA） on the adhesion, migration, and invasion ovarian cancer cells. Methods Human ovarian cancer cells of the lines SKOV3 and OVCAR3 were cultured. Suspensions of SKOV3 and OVCAR3 cells were treated with DHA of the concentrations of 0. 5,2. 5,12. 5, and 62. 5 μmol/L respectively, and then inoculated on the plate coated with Matrigel. MTr method was used to -determine the adhesion rate. Transwell membrane chamber model was used to evaluate the effect of DHA on the migration and invasion of the SKOV3 and OVCAR3cells. Western blotting and reverse transcriptase polymerase chain reaction were used to detect the effect of DHA on the phosphoralytion of focal adhesion kinase （FAK） and on the effect of expression of metal matrix proteinases （MMPs） and their tissue inhibitors （TIMPs） respectively. Results （ 1 ） Compared to the cells without DHA treatment, the cell adhesion ability levels of the SKOV3 and OVCAR3 cells treated with 12.5 μmol/L DHA decreased by 76. 1% and 57. 9% respectively （P 〈 0.05）, while their migration ability levels decreased by 59. 3% and 69.7% respectively （ P 〈 0. 05 ）. （2） Both SKOV3 and OVCAR3 showed weak invasion ability, and DHA only showed a slight inhibitory effect on the cell invasion of these 2 lines （ both P 〉 0. 05）. （3） Compared to the cells without DHA treatment, the phosphorylation level of FAK of the SKOV3 and OVCAR3 cells treated with 12. 5 μmol/L DHA decreased by 42. 9% and 44. 8% respectively （both P〈0. 05）. （4） RT-PCR showed mRNA expression of MMP2, TIMP1, and TIMP2, but not mRNA expression of MMP9 in both SKOV3 and OVCAR3 cells. The mRNA expression levels of the SKOV3 and OVCAR3 cells treated with 12. 5 μmol/L DHA increased by 1.5 and 2. 6 times respectively （ both P 〈 0. 05）. Conclusion DHA has inhibitory effects on the adhesion and migration of epithelial ovarian cancer cells, which may be related to its down-regulation of the phosphorylation of FAK in th

关 键 词：双氢青蒿素 卵巢肿瘤 生物学行为 基质金属蛋白酶 基质金属蛋白酶组织抑制因子 

分 类 号：R686[医药卫生—骨科学]