异硫氰酸苯已酯抑制骨髓瘤细胞Notch信号表达的研究

摘要

为了研究异硫氰酸苯已酯(phenylhexyl isothiocyanate,PHI)在体外对骨髓瘤细胞RPM18226增殖抑制的分子机制,用不同浓度PHI与RPMI8226细胞共同孵育,用MTT比色法检测PHI处理后细胞增殖抑制;用DAPI染色现察PHI处理后细胞凋亡;Westem blot检测PHI处理后瘤细胞Notch1、Jagged2、BCL-2和P-Akt蛋白表达变化.结果显示,PHI在一定浓度范围内能抑制瘤细胞增殖,诱导瘤细胞凋亡,其抑制效应具有时间和浓度依赖性.PHI可以下调瘤细胞中Notchl和Jagged2蛋白的表达并呈时间和浓度依赖性,同时降低BCL-2和p-Akt的表达.结论:PHI在体外能够抑制骨髓瘤细胞增殖,诱导细胞凋亡;细胞凋亡的发生与PHI抑制Notch信号及其下游靶基因p-Akt和BCL-2的表达有关,PHI可能成为新一代的Notch信号抑制剂,是一种潜在的骨髓瘤治疗药物.%In order to investigate the mechanisms of phenylhexyl isothiocyanate (PHI) inhibiting the proliferation of multiple myeloma cell RPMI8226 in vitro, the RPMI8226 cells were co-cultured with PHI of various concentrations. The inhibition of proliferation wase measured by MTT test and the cell apoptosis was assayed by DAPI staining. The changes of Notch1, Jagged2, BCL-2 and p-Akt proteins in the PHI-treated cells were detected by Western blot. The results showed that PHI inhibited RPMI8226 cell proliferation in certain concentration range and induced their apoptosis. The inhibiting effect caused by PHI showed a concentration- and time-dependent manner. The PHI decreased expressions of Notch1 and Jagged2 proteins in a concentration- and time-dependent manners, the levels of BCL-2 and p-Akt declined at the same time. It is concluded that PHI can inhibit proliferation of RPMI8226 cells, and induce their apoptosis. The cell apoptosis is associated with the inhibition of Notch signaling and downstream targets BCL-2 and p-Akt proteins of RPMI8226 cells, PHI may be a new Notch signaling inhibitor and a promising therapeutic drug for multiple myeloma.