三氧化二砷对人卵巢癌耐药细胞株细胞增殖和转移能力的影响  

Impact of Arsenic Trioxide on Prolif eration and Metastasis of Drug-Resistant Human Ovarian Carcinoma Cell Line

作　　者：黄守国[1] 孔北华[2] 马玉燕[2] 江森[2] 

机构地区：[1]山西医科大学第二医院妇产科,山西太原030001 [2]山东大学齐鲁医院妇产科,山东济南250012

出　　处：《癌症》2002年第8期863-867,共5页Chinese Journal of Cancer

摘　　要：背景与目的:卵巢恶性肿瘤细胞对顺铂的耐药性及早期发生转移严重影响着卵巢恶性肿瘤患者的化疗效果。本研究探讨三氧化二砷(arsenictrioxide,As2O3)对人卵巢癌耐药细胞株3AO/cDDP细胞增殖和转移能力的影响及其机制。方法:采用四甲基偶氮唑蓝(MTT)法检测不同浓度As2O3对3AO/cDDP细胞的生长抑制率;采用流式细胞技术(FCM)检测As2O3对细胞凋亡率、细胞周期以及Fas、N-myc基因和nm23H1、MTA1基因表达的影响。所有结果均与对照组比较。采用透射电镜技术观察As2O3作用后3AO/cDDP细胞的形态变化。结果:As2O3明显抑制3AO/cDDP细胞的增殖,抑制作用呈时间和剂量依赖性(P<0.05)。在一定浓度范围内,3AO/cDDP细胞凋亡率与As2O3的浓度和作用时间呈依赖关系,诱导凋亡的最适浓度是3μmol/L。低浓度As2O3作用下,3AO/cDDP细胞周期S期通过受阻,高浓度时诱导S期细胞凋亡;As2O3作用后,两种细胞株Fas和nm23H1基因的表达均上调,N-myc和MTA1基因的表达均下调,差异均有显著性(P>0.05);形态学观察可看到As2O3作用后3AO/cDDP形成典型的凋亡小体。结论:As2O3通过上调Fas、nm23H1和下调N-myc、MTA1基因的表达,有效地降低人卵巢癌耐药细胞株细胞的增殖和转移能力。Background &Objective:The drug-resistance and metastasis in early stages of human malignant ov arian neoplasm have significant effect on chemotherapy of human ovarian carcinoma.The objective of this study was to explore the impact of arsenic trioxide(As 2 O3 )on proliferation and metastasis of d rug-resistant human epithelial ova rian carcinoma cell line 3AO /cDDP,in order to treat human ovarian carcinoma thoroughly.Methods:The growing inhibiting rates of drug-resistant human ovarian carcinoma cell line 3AO /cDDP by various co ncentrations of As 2 O 3 in different time course were studied by methyl thiazolyl tetrazo lium(MTT)method;Apoptosis percentage,cell cycle phase distribution and expressions of Fas,N-myc,nm23H 1 and MTA1gene were estimated by flow c ytometry(FCM);3AO /cDDP cells apoptosis phenotyp e was observed by transmissional electro n microscopy.Result:3AO /cDDP cell growing inhibiting ra tes by As 2 O 3 were significantly different in dose-dependent and tim e-dependent manners(P<0.05);Within a certain concentration ran ge,3AO /cDDP apoptosis inducing rates by As 2 O 3 were dose-and time-dependent,and t he most appropriate concentration w as 3.0μmol /L.Lower concentrations of As 2 O 3 perturbed cell progressing through S /G2phase,while higher concentrations selectively induced S phase cells apoptosis;As 2 O 3 up-regulated Fas and nm23H 1 gene expressions,but down-regulated N-myc and MTA1gene expressions.Morphologic al observation indicated that As 2 O 3 inducing 3AO /cDDP death characterized by apoptotic phenotype.Conclusion:As 2 O 3 could influence the capacity of grow th and proliferation of drug-resistant human ovarian carcinoma cell line and its mechanism could be positively and negatively related with Fas,nm23H 1 gene and N-Myc,MTA1gene expressions.

关 键 词：三氧化二砷 卵巢肿瘤细胞 抗药性 凋亡 转移 

分 类 号：R737.31[医药卫生—肿瘤]