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Asiatic acid, a triterpene, inhibits cell proliferation through regulating the expression of focal adhesion kinase in multiple myeloma cells

机译:三萜亚硫酸通过调节多发性骨髓瘤细胞中粘着斑激酶的表达来抑制细胞增殖

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摘要

The aim of the present study was to investigate whether asiatic acid (AA), a pentacyclic triterpene derived from Centella asiatica, exerts anti-proliferative effects on multiple myeloma RPMI 8226 cells and to determine the molecular mechanism underlying the anticancer action of AA. The study sought to analyze the potential role of AA on the proliferation of the RPMI 8226 cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium assay. Cell cycle arrest was detected by flow cytometry, and the expression levels of focal adhesion kinase (FAK) in the myeloma cells induced by AA were analyzed using the western blotting and immunoprecipitation methods. The results indicated that AA significantly inhibited cell proliferation in a time- and dose-dependent manner and led to G2/M phase arrest at concentrations of 35 and 40 μmol/l in the RPMI 8226 cells. The expression levels of FAK and p-FAK were distinctly decreased following AA treatment (at the concentration of 40 μmol/l) for 24 h compared with that of the control groups. Taken together, these results demonstrated that AA was able to regulate cell cycle progression in RPMI 8226 cells, thereby significantly inhibiting cell growth. Furthermore, AA decreased the expression levels of FAK, indicating that the antitumor mechanism of AA may be associated with the inhibition of signal transduction mediated by FAK.
机译:本研究的目的是研究积雪草中的五环三萜积雪草酸(AA)是否对多发性骨髓瘤RPMI 8226细胞发挥抗增殖作用,并确定AA的抗癌作用的分子机制。该研究试图使用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑鎓分析法分析AA对RPMI 8226细胞增殖的潜在作用。流式细胞术检测细胞周期停滞,并用western blotting和免疫沉淀法分析AA诱导的骨髓瘤细胞中黏着斑激酶(FAK)的表达水平。结果表明,AA在RPMI 8226细胞中浓度为35和40μmol/ l时,以时间和剂量依赖性方式显着抑制细胞增殖,并导致G2 / M期停滞。与对照组相比,AA处理24 h后,FAK和p-FAK的表达水平明显降低(浓度为40μmol/ l)。综上,这些结果表明,AA能够调节RPMI 8226细胞中的细胞周期进程,从而显着抑制细胞生长。此外,AA降低了FAK的表达水平,表明AA的抗肿瘤机制可能与FAK介导的信号转导的抑制有关。

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