双氢青蒿素对卵巢癌生长的抑制作用及其机制的研究

目的研究双氢青蒿素对体内外卵巢癌生长的抑制作用及其机制。方法双氢青蒿素卵巢癌细胞株HO-8910PM 24h后,CCK-8法检测细胞增殖;ELISA法检测细胞凋亡;以DCFH-DA为荧光探针检测卵巢癌细胞内活性氧(reactiveoxygen species,ROS)水平;Western blotting检测卵巢癌细胞中keap1蛋白、胞核Nrf2蛋白的表达;建立起裸鼠卵巢癌皮下移植瘤模型,免疫组织化学法检测肿瘤组织中超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxi-dase,GPX)的阳性表达。结果与对照组相比,双氢青蒿素可明显抑制体外卵巢癌细胞生长,并明显诱导细胞凋亡;双氢青蒿素可显著下调卵巢癌细胞胞核卵巢癌蛋白表达,而促进细胞内Keap1蛋白表达;化学显示法结果显示,双氢青蒿素使卵巢癌细胞SOD、GPX的活性明显降低;双氢青蒿素亦可明显降低卵巢癌肿瘤组织中SOD和GPX的阳性表达。结论双氢青蒿素可显著抑制卵巢癌细胞的生长,该作用可能通过Nrf2-Keap1信号通路来促进卵巢癌细胞内活性氧的产生,进一步促进细胞凋亡。

Anti-tumor Effect of DHA on Ovarian Cancer and its Mechanism

Objective To explore the effect of DHA in the growth inhibition of ovarian cancer cells and the mechanism.Methods After human ovarian cancer cells HO-8910PM were treated with DHA for 24h,cell growth was determined by the Cell Counting Kit-8(CCK-8) assay and apoptosis was evaluated by ELISA.Intracellular ROS in ovarian cancer cells was detected by 2,7-dichlorofluorescein diacetate(DCFH-DA) as a fluorescent probe.The expression of keap1 protein and nuclear Nrf2 protein in ovarian cancer cells was analyzed by Western blot assay.HO-8910PM cells were injected subcutaneously into nude mice to establish xenograft model.Immunohistochemistry was used to detect the positive expression of SOD and GPX in the tumors.Results Compared with control group,the proliferation of ovarian cancer cells was inhibited markedly by DHA.Apoptosis rate induced by DHA was significantly highter than that of control.DHA can obviously decrease the expression of nuclear Nrf2 protein,but significantly increase the expression of keap1 protein.The levels of SOD and GSH-PX in ovarian cancer cells after treatment of DHA were obviously lower than those in control group.The positive expression of SOD and GPX was both decreased in tumors after administration of DHA.Conclusion DHA can inhibit the proliferation of ovarian cancer cells,through the Nrf2-keap1 signaling pathway,increasing intracellular oxidative stress and promoting apoptosis.