冬凌草甲素介导Notch信号通路对多发性骨髓瘤细胞生长水平、凋亡率及异常转化情况研究

Study on the growth leveland apoptotic rate and abnormal transformation of multiple myeloma cells by oridonin-mediated Notch signaling pathway

目的探究冬凌草甲素介导Notch信号通路对多发性骨髓瘤细胞生长水平、凋亡率及异常转化情况。方法选取U266细胞、RPMI8226细胞和KAS-6/1细胞,采用CCK8法检测细胞生长水平,采用酶标仪492 nm处检测光密度检测物厚度D值测定细胞的生长抑制率,随后采用流式细胞仪检测RPMI8226细胞和U266细胞的凋亡情况,最后对所检测细胞进行异常转化的观察。结果研究组U266细胞、RPMI8226细胞和KAS-6/1细胞的生长水平均明显低于对照组(P<0.05)。研究组干预后Notch 1-siRNA与核因子κB(NF-κB)-siRNA表达水平变化明显优于对照组(P<0.05)。研究组RPMI8226细胞、U266细胞凋亡率明显优于对照组(P<0.05)。研究组异常转染、异常克隆、异常增生的发生率明显低于对照组(P<0.05)。结论冬凌草甲素能够明显抑制多发性骨髓瘤U266细胞、RPMI8226细胞、KAS-6/1细胞体外生长,有效激活Notch信号通路调节诱导肿瘤细胞凋亡过程,值得临床推广应用。

Objective To investigate the effects of oridonin-mediated Notch signaling pathway on the growth level,apoptosis rate,and abnormal transformation of human multiple myeloma cells.Methods U266 cells,RPMI8226 cells and KAS-6/1 cells were induced with blank control or oridonin.Cell viability was measured by CCK-8 assay.Cell growth inhibition was measured by detecting optical density at 492 nm wavelength using a microplate reader.Flow cytometry was performed to examine the apoptosis of RPMI8226 and U266 cells.Abnormal transformation of the detected cells was observed.Results Cell growth was significantly lower in U266 cells,RPMI8226 cells and KAS-6/1 cells treated with oridonin than those of controls(P<0.05).Expression levels of Notch 1 and NF-κB siRNA were significantly upregulated in U266 cells,RPMI8226 cells and KAS-6/1 cells treated with oridonin than those of controls(P<0.05).A higher apoptotic rate was detected in oridonin-induced RPMI8226 and U266 cells in comparison to controls(P<0.05).The incidences of abnormal transfection,colony formation and proliferation were significantly lower in U266 cells,RPMI8226 cells and KAS-6/1 cells treated with oridonin than those of controls(P<0.05).Conclusion Oridonin can significantly inhibit the growth of U266 cells,RPMI8226 cells and KAS-6/1 cells in vitro,and effectively activate Notch signaling pathway and induce apoptosis of tumor cells,which is worthy of clinical application.