辛二酰苯胺异羟肟酸联合紫杉醇对卵巢癌细胞OC3杀伤与自噬的影响

摘要

目的：研究辛二酰苯胺异羟肟酸（ suberoylanilide hydroxamic acid，SAHA）与紫杉醇（ paclitaxel，PTX）联合应用对人卵巢癌细胞OC3杀伤及自噬的影响，探讨两药联合是否具有协同作用。方法利用SAHA和（或） PTX处理OC3细胞后，倒置显微镜下观察细胞形态；四甲基偶氮唑蓝（ MTT）检测细胞的生长状态； AO／EB双染色观察细胞是否出现自噬泡，析因方差法与金式公式法分析联合用药效果。结果 SAHA和PTX单独或联合用药处理后，倒置显微镜下可见联合用药组细胞形态较单独用药组发生显著改变，细胞大部分出现折光率差和死亡的现象；MTT法检测细胞增殖结果表明，联合用药组较单独用药组显著抑制OC3细胞的增殖与存活（P＜0．05）；析因方差分析显示，两药存在正交互作用，金式公式计算表明两药具有协同效应；AO／EB双染色发现各组细胞出现自噬现象，且联合用药组诱导自噬的发生率显著高于单独用药组。结论 SAHA联合PTX对人卵巢癌细胞OC3具有明显的协同杀伤作用，并可诱导其发生自噬。%Objective To evaluate the effect of suberoylanilide hydroxamic acid(SAHA) or/and paclitaxel(PTX) on lethality and autophagy of human ovarian cancer OC3 cells,and to explore whether the combination of the two drugs has a synergistic function.Methods The morphology of OC3 cells was treated with SAHA and/or PTX, and then the morphology of treated OC3 cells was observed under an inverted microscope, cell proliferation was detected by MTT assay and autoph-agy was analyzed by AO/EB double staining assay.The synergistic effect of SAHA and/or PTX was analyzed by factorial design and gold formula method.Results After treatment with SAHA and/or PTX, the morphology of OC3 cells in the combination group ( SAHA+PTX) displayed significant morphological changes.OC3 cells became less adherent and refrac-tive than in other groups.Cell proliferation by MTT assay demonstrated that the growth inhibition rate of the combination groups was higher than in groups treated with SAHA or PTX respectively( P<0.05) .Furthermore, the synergistic effect af-ter treatment with a combination of SAHA with PTX was proved by the factorial design and gold formula method.The auto-phagy rate of the combined groups was significantly higher than in single treatment groups (P<0.05) by AO/EB double staining.Conclusion SAHA and PTX can inhibit the survival of OC3 cells and induce its autophagy.The two drugs have synergistic antitumor effects.