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目的研究辛二酰苯胺异羟肟酸(suberoylanilide hydroxamic acid,SAHA)与紫杉醇(paclitaxel,PTX)单独及联合应用对人卵巢癌紫杉醇耐药细胞OC3/P存活及凋亡的影响,初步探讨两种药物联合应用是否具有协同作用。方法采用倒置显微镜观察不同药物处理对细胞形态的影响;用四甲基偶氮唑蓝(MTT)比色法测定各组细胞生长抑制情况;流式细胞仪AnnexinⅤ-FITC/PI法检测各组细胞凋亡率,并进行联合用药分析。结果不同药物处理后,倒置显微镜下可见细胞形态发生改变,联合用药组形态变化较单独用药组显著;MTT法检测细胞生长情况,结果显示,联合用药组较单独用药组具有显著抑制OC3/P细胞存活的作用(P<0.05),析因设计方差分析显示,两药物存在正交互作用,并由金式公式计算表明两药物具有协同作用。进一步利用流式细胞术检测各组细胞凋亡情况,结果表明,联合用药组诱导凋亡的比率显著高于单药组,且差异具有统计学意义(P<0.05)。结论 SAHA联合PTX可有效抑制人卵巢癌紫杉醇耐药细胞OC3/P的存活并诱导其凋亡,两药物联合有协同效应。
Objective To investigate the effects of suberoylanilide hydroxamic acid (SAHA) and paclitaxel (PTX) alone and in combination on the survival and apoptosis of human ovarian cancer cell line paclitaxel-resistant OC3 / P, Is the combination of drugs synergistic? Methods The morphological changes of cells treated with different drugs were observed by inverted microscope. The growth inhibition of cells in each group was determined by MTT colorimetric assay. The cells were analyzed by flow cytometry with AnnexinⅤ-FITC / PI Apoptosis rate, and the combination of drug analysis. Results The morphological changes of the cells were observed under inverted microscope after treatment with different drugs. The morphological changes of the combination group were more significant than those of the drug alone group. The cell growth was detected by MTT assay. The results showed that OC3 / P cells (P <0.05). Analysis of factorial design ANOVA showed that there was an orthogonal interaction between the two drugs and the gold formula showed that the two drugs had a synergistic effect. Flow cytometry was used to detect the apoptosis of each group. The results showed that the apoptosis rate of the combination group was significantly higher than that of the single drug group, and the difference was statistically significant (P <0.05). Conclusions SAHA combined with PTX can effectively inhibit the survival and induce apoptosis of OC3 / P cells in paclitaxel resistant human ovarian cancer cells. The combination of the two drugs has synergistic effect.