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机构地区:[1]华中科技大学同济医学院附属协和医院,湖北武汉430022 [2]河北省人民医院,河北石家庄050051
出 处:《实用妇产科杂志》2005年第12期728-731,共4页Journal of Practical Obstetrics and Gynecology
基 金:国家自然科学基金资助项目(30070786)
摘 要:目的:探讨凋亡抑制基因NF-κB、Survivin对卵巢癌细胞株耐药性的诊断价值。方法:采用卵巢上皮性癌细胞株A2780和由此细胞株诱导的耐顺铂细胞株AD4,分别加入顺铂(DDP)和紫杉醇(Taxol),并设空白对照,测定两组细胞中凋亡抑制基因核因子(NF-κB)、Survivin和多耐药基因(Mdr1)mRNA的表达;同时检测各组细胞的凋亡率。结果:经DDP处理后,Mdr1在两株细胞中均无明显表达,与G3PDH的比值均低于0.1;而Taxol作用后,Mdr1在两株细胞中表达均增加,与G3PDH的比值分别为1.98和1.86,但差异无显著性。NF-κB在各组细胞中均有表达,各组之间差异无显著性。Survivin有较强表达,与G3PDH的比值为4.5,耐药细胞株的比值为6.9。在两细胞株的不同实验中,Mdr1的表达与凋亡率无明显相关性,而Survivin则是负相关(P<0.05,r=-0.89)。结论:在卵巢癌及卵巢癌耐顺铂细胞株中,紫杉醇可诱导Mdr1高表达,而DDP对Mdr1表达无影响;NF-κB主要是通过活性增加,促进Mdr1表达来诱发卵巢癌细胞耐药;Survivin的表达与细胞凋亡率呈负相关,提示Survivin可作为肿瘤细胞耐药检测指标之一。Objective: To investigate the role of apoptosis inhibiting genes, nuclear factor (NF-κB) and Survivin, in multidrug resistance (Mdr) in ovarian cancer cell lines after exposed to chemotherapy agent. Methods: Human epithelial ovarian cancer cell line A2780 and its platinum (DDP) - resistance cell line AD4 was used. The experiment divided into three groups: blank group (no chemotherapy agent treatment), DDP group (treatment with DDP), and Taxol group (treatment with Taxol). Expression of NF-κB, mdrl and Survivin genes in each group was detected by using Reverse transcdption-polyrnerase chain reaction (RT- PCR). G3 PDH was used as internal for semi quantitative analysis. Apsptosis in the ovarian cancer cell lines was measured by flow cytometry. Results: After treated by DDP and Taxol for 48 hours, no significant difference of NF - κB expression was observed in both cell lines. The higher expression of Mdrl in drug- sensitive cell line and DDP- resistant cell line was detected only after treatment with Taxol for 48 hours, separately, but had no significantly difference between them. Survivin expression was higher in the sensitive ovarian cancer cell line than fn the drug - resistant cell line. Expression of Survivin had an apparent negative correlation with apoptosis rate ( P〈0.05, r= -0.89), while no linear relation was observed between the expression of Wdrl and apoptosis rate. Conclusions: The expression of Survivin gene did present in ovarian cancer cell lines, Survivin and NF-κB may be involved in the mechanism of muitidrug resistance, The findings in the study may elucidate the possibility of providing good background target gene therapy of multidrug in ovarian cancer.
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