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

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。

Impact of arsenic trioxide on proliferation and metastasis of drug-resistant human ovarian carcinoma cell line

BACKGROUND & OBJECTIVE: The drug-resistance and metastasis in early stages of human malignant ovarian neoplasm have significant effect on chemotherapy of human ovarian carcinoma. The objective of this study was to explore the impact of arsenic trioxide(As2O3) on proliferation and metastasis of drug-resistant human epithelial ovarian 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 concentrations of As2O3 in different time course were studied by methyl thiazolyl tetrazolium (MTT) method; Apoptosis percentage, cell cycle phase distribution and expressions of Fas, N-myc, nm23H1 and MTA1 gene were estimated by flow cytometry (FCM); 3AO/cDDP cells apoptosis phenotype was observed by transmissional electron microscopy. RESULTS: 3AO/cDDP cell growing inhibiting rates by As2O3 were significantly different in dose-dependent and time-dependent manners(P < 0.05); Within a certain concentration range, 3AO/cDDP apoptosis inducing rates by As2O3 were dose- and time-dependent, and the most appropriate concentration was 3.0 mumol/L. Lower concentrations of As2O3 perturbed cell progressing through S/G2 phase, while higher concentrations selectively induced S phase cells apoptosis; As2O3 up-regulated Fas and nm23H1 gene expressions, but down-regulated N-myc and MTA1 gene expressions. Morphological observation indicated that As2O3 inducing 3AO/cDDP death characterized by apoptotic phenotype. CONCLUSION: As2O3 could influence the capacity of growth and proliferation of drug-resistant human ovarian carcinoma cell line and its mechanism could be positively and negatively related with Fas, nm23H1 gene and N-Myc, MTA1 gene expressions.