青蒿琥酯对卵巢癌细胞侵袭活力、蛋白酶及Th1/Th2细胞因子表达的影响

Effects of artesunate on invasion,protease and Th1/Th2 cytokines expression in ovarian cancer cells

目的 研究青蒿琥酯(ART)对卵巢癌细胞侵袭活力、蛋白酶及Th1/Th2细胞因子表达的影响。方法 选择卵巢癌SKOV-3细胞株进行培养并分为空白对照组(不含药物的DMEM基处理)和不同剂量ART组(含12. 5μg/ml、25μg/ml、50μg/ml、100μg/ml ART的无血清DMEM处理)。处理24 h后,测定细胞侵袭数目、细胞中蛋白酶[基质金属蛋白酶2(MMP2)、MMP9]及其抑制分子[金属蛋白酶组织抑制物1(TIMP1)、TIMP2、TIMP3]的表达量、Th1/Th2细胞因子的含量。结果 不同剂量ART组的细胞侵袭数目、MMP2及MMP9的m RNA表达量、IL-4及IL-10的含量均明显低于空白对照组,TIMP1、TIMP2、TIMP3的m RNA表达量以及IL-2、IFN-γ的含量均明显高于空白对照组(P <0. 05)。其中100μg/ml ART组的细胞侵袭数目为47. 61±8. 83,MMP2及MMP9的m RNA表达量分别为(0. 46±0. 08)及(0. 50±0. 07),IL-4及IL-10的含量分别为(49. 44±6. 58) pg/ml及(25. 42±3. 48) pg/ml,明显低于其他各组(P <0. 05);TIMP1、TIMP2、TIMP3的m RNA表达量分别为(2. 03±0. 38)、(1. 83±0. 29)、(1. 77±0. 35),IL-2、IFN-γ的含量分别为(7. 03±1. 08) ng/ml、(2. 09±0. 38) ng/ml,均明显高于其他剂量ART组(P <0. 05)。结论 ART用于卵巢癌细胞的干预能够降低细胞侵袭活力、抑制蛋白酶表达、调节Th1/Th2细胞因子分泌,具有抗卵巢癌活性,且上述作用呈剂量依赖性。

Objective To study the effect of artesunate(ART)on invasion activity,protease and Th1/Th2 cytokine expression in ovarian cancer cells.Methods SKOV-3 cells were cultured and divided into control group and ART group(12.5μg/ml,25μg/ml,50μg/ml,100μg/ml).After 24 hours of treatment,the number of cell invasion,the expression of protease and its inhibitor,and the content of Th1/Th2 cytokines were measured.Results The number of invasive cells,the mRNA expression of MMP2 and MMP9,the contents of IL-4 and IL-10 in ART group were significantly lower than those in control group.The expression of TIMP1,TIMP2 and TIMP3 mRNA,the content of IL-2 and IFN-γin ART group were significantly higher than those in control group(P<0.05).The number of invasive cells in 100μg/ml ART group was 47.61±8.83,the mRNA expression of MMP2 and MMP9 were 0.46±0.08 and 0.50±0.07,the contents of IL-4 and IL-10 were 49.44±6.58 pg/ml and 25.42±3.48 pg/ml,which were significantly lower than those in other groups(P<0.05).The contents of IL-2 and IFN-γwere(7.03±1.08)ng/ml,(2.09±0.38)ng/ml,which were significantly higher than those of other groups(P<0.05).Conclusion ART for intervention of SKOV-3 cells can inhibit the expression of protease and Th1/Th2 cytokine secretion in ovarian cancer cells,and has anti-ovarian cancer activity.