[Atractylenolide I Can Induce Apoptosis of U266 Cells and Enhance Bortezomib Effect]

Autor: Zi-Xin, Mai, Tian-Qi, Yu, Ting-Ting, Fan
Rok vydání: 2020
Předmět:
Zdroj: Zhongguo shi yan xue ye xue za zhi. 28(1)
ISSN: 1009-2137
Popis: To investigate the effect of atractylenolide I on proliferation and apoptosis of U266 cells, and anti-multiple myeloma effect of bortezomib.Bortezomib, bortezomib combined atractylenolide I and atractylenolide I at different concentrations were added into U266 cells respectively, cellular proliferation toxicity was evaluated by CCK-8 assay, apoptosis and cell cycle were detected by using flow cytometry with Annexin V-FITC/PI staining. RT-PCR and Western blot analysis were used to detect the mRNA and protein levels of targeting gene Caspase-3,Caspase-9,BCL-2,BAX,JAK2,STAT3 and IL-6, respectively.The proliferation of U266 cells could inhibited by atractylenolide I, and the apoptosis of U266 cells could be promoted by atractylenolide I, also, which showed a dose-dependent manner(P0.00; r=0.99). Moreover, the atractylenolide I could regulat the mitochondrial pathway(P0.01). The combination of 2 drugs could strengther the inhibition of U266 cell proliferation significantly, and the expression level of IL-6,JAK2,STAT3 and BCL-2 mRNA and protein could be decreased by single drug and 2 drugs both(P0.01).Atractylenolide I significantly inhibits the proliferation of U266 cells and promotes their apoptosis. At the same time, it acts synergistically with bortezomib, which may be related to mitochondrial pathway, and probably related to the regulating of IL-6, JAK2 and STAT3 gene expression in signal pathway of JAK2/STAT3.白术内酯I能诱导U266细胞凋亡和增强硼替佐米的作用.探讨白术内酯I对U266细胞增殖和凋亡的作用及其对硼替佐米抗多发性骨髓瘤的作用.分别将不同浓度的白术内酯I、硼替佐米以及硼替佐米+白术内酯I作用于U266细胞,并应用CCK-8法检测细胞增殖活性,Annexin V-FITC/PI染色及流式细胞术检测细胞凋亡率及细胞周期,应用RT-PCR及Western blot分别检测目标基因Caspase-3、Caspase-9、BCL-2、BAX、JAK2、STAT3及IL-6的mRNA及相应蛋白的表达.白术内酯I能呈浓度依赖性抑制U266细胞的增殖(r=-0.98)和促进细胞凋亡(r=0.99),调控线粒体介导的凋亡途径;联合用药能显著增强对细胞增殖的抑制作用(P0.01);同时,单药组及联合用药组均能显著降低IL-6、JAK2、STAT3及BCL-2 mRNA及蛋白表达水平(P0.01).白术内酯I能显著抑制U266细胞增殖,促进其凋亡,并能与硼替佐米产生协同作用,此作用与线粒体凋亡途径有关,可能与调节JAK2/STAT3通路上的IL-6、JAK2、STAT3等基因表达有关.
Databáze: OpenAIRE