小白菊内酯增强伏立诺他抑制非小细胞肺癌A549细胞增殖的机制

The mechanism of parthenolide strengthen vorinostat on inhibiting the proliferation of A549 non-small cell lung cancer cells

本研究考察了小白菊内酯(parthenolide,PTL)与组蛋白去乙酰化酶抑制剂伏立诺他(vorinostat,suberoylanilide hydroxamic acid,SAHA)对非小细胞肺癌A549增殖的协同作用及作用机制。采用CCK-8(cell counting kit-8)和集落形成实验检测PTL和SAHA的协同作用和细胞增殖情况;细胞划痕实验检测A549细胞的迁移能力;Annexin V-FITC/PI(fluorescein isothiocyanate isomer/propidium iodide)流式细胞术实验和Western blot实验检测细胞凋亡情况并探索抗肿瘤作用机制。结果表明,PTL和SAHA通过协同作用增强了对A549细胞的增殖和迁移的抑制作用,且联合用药组抑制作用明显强于单药组。PTL协同SAHA通过调节p53和c-myc通路诱导细胞凋亡,影响凋亡相关蛋白PARP(poly ADP-ribose polymerase)、caspase-9(cysteinyl aspartate specific proteinase-9)和caspase-3的表达。上述研究结果表明,PTL与SAHA联合用药具有协同作用,可诱导A549细胞凋亡并抑制细胞的增殖,对非小细胞肺癌治疗新方法的研究具有潜在价值。

This research explored the synergistic effects and the mechanism of parthenolide(PTL)and vorinostat(suberoylanilide hydroxamic acid,SAHA)on the proliferation of A549 non-small cell lung cancer cells.The combination effect of PTL and SAHA was detected by cell counting kit-8(CCK-8)and colony formation assays.Scratch test was performed to detect cell migration.Annexin V-fluorescein isothiocyanate isomer/propidium iodide(FITC/PI)flow cytometry and Western blot analyses were used to determine cell apoptosis and its mechanism.The results showed that combination of PTL and SAHA inhibited the proliferation and migration of A549 with a synergistic effect compared to the single-drug groups.The combination of PTL and SAHA had synergistic effect to induce cell apoptosis by regulating p53 and c-myc pathways,and affected the expression levels of poly ADP-ribose polymerase(PARP),cysteinyl aspartate specific proteinase(caspase)-9,and caspase-3.Taken together,this study shows that combination of PTL and SAHA has synergistic effect,induces cell apoptosis and inhibits A549 proliferation,which is likely to be a novel strategy for the treatment of non-small cell lung cancer.