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目的:探讨解聚素金属基质蛋白酶10(ADAM10)抑制剂GI254023X对多发性骨髓瘤H929细胞增殖与凋亡的影响及其作用机制。方法:选择不同浓度GI254023X处理H929细胞,CCK-8法检测并绘制增殖抑制曲线,Annexin V/7-AAD双染流式细胞术检测细胞存活与凋亡,Western blot检测切割后的Notch1蛋白(Cleaved Notch1),定量PCR检测Notch1靶基因Hes-1的转录变化。结果:GI254023X能明显抑制H929细胞增殖,随着药物浓度的增大及时间的延长,细胞的增殖能力逐渐下降;GI254023X能够诱导H929细胞凋亡;Western blot检测结果显示,Cleaved Notch1在GI254023X作用后水平下降;GI254023X能够使Hes-1基因的表达减低。结论:GI254023X能抑制H929细胞增殖并诱导其凋亡,其机制可能与抑制Notch1活化有关。
OBJECTIVE: To investigate the effect and mechanism of glibenclamide 10 (ADAM10) inhibitor GI254023X on proliferation and apoptosis of multiple myeloma H929 cells. Methods: H929 cells were treated with different concentrations of GI254023X, proliferation inhibition curve was detected by CCK-8 assay and cell proliferation inhibition curve was drawn. Annexin V / 7-AAD double staining flow cytometry was used to detect cell survival and apoptosis. Western blot was used to detect cleaved Notch1), quantitative PCR detection of Notch1 target gene Hes-1 transcriptional changes. Results: GI254023X could significantly inhibit the proliferation of H929 cells. The proliferation of H929 cells decreased gradually with the increase of drug concentration and time, and GI254023X induced the apoptosis of H929 cells. Western blot showed that Cleaved Notch1 Decreased; GI254023X can reduce the expression of Hes-1 gene. Conclusion: GI254023X can inhibit the proliferation and induce the apoptosis of H929 cells, which may be related to the inhibition of Notch1 activation.