论文部分内容阅读
本研究旨在探讨姜黄素(curcumin)联合硼替佐米(bortezomib)对人多发性骨髓瘤(multiple myeloma,MM)细胞系H929细胞增殖和凋亡的影响,并进一步探讨其作用的相关机理。采用MTT法检测不同浓度的姜黄素和硼替佐米单用或联合应用对H929细胞的增殖抑制作用;采用流式细胞术(FCM)分析单用和联合用药时细胞的凋亡比率;采用RT-PCR法分析凋亡相关基因BCL-2、BAX及细胞周期相关蛋白cyclin D1的表达变化;采用免疫荧光染色法测定不同处理组NF-κB P65蛋白的分布变化。结果表明:姜黄素和硼替佐米单用及联合应用时均可抑制H929细胞的生长,呈剂量依赖性,联合用药在一定浓度范围内有协同效应;联用组细胞凋亡的比例明显高于单用组及对照组;与单用组相比,联用组cyclin D1,BCL-2基因表达下降,BAX升高。核因子NF-κB P65在单用组的胞核内的表达减弱,联合应用组NF-κB P65蛋白分布于胞浆。结论 :姜黄素与硼替佐米均可抑制H929细胞的生长增殖、促进凋亡,联合应用有协同效应。抑制核因子NF-κB的转录及影响其调节凋亡相关基因可能是作用机制之一。
This study aimed to investigate the effects of curcumin combined with bortezomib on the proliferation and apoptosis of human multiple myeloma (MM) cell line H929 and to explore the underlying mechanisms. The inhibitory effects of curcumin and bortezomib at different concentrations on the proliferation of H929 cells were detected by MTT assay. The apoptosis rates of cells were detected by flow cytometry (FCM) PCR was used to analyze the expression of apoptosis-related genes BCL-2, BAX and cyclin D1. The distribution of NF-κB P65 protein in different treatment groups was detected by immunofluorescence staining. The results showed that both curcumin and bortezomib could inhibit the growth of H929 cells both in a dose-dependent manner and in combination with bortezomib at a certain concentration range. The apoptosis rate in combination group was significantly higher than that in combination group Single group and control group. Compared with the single group, the expression of cyclin D1 and BCL-2 gene decreased and BAX increased. The expression of nuclear factor NF-κB P65 was weakened in the nucleus of single-use group, while the combination of NF-κB P65 protein was distributed in the cytoplasm. CONCLUSION: Both curcumin and bortezomib can inhibit the growth and proliferation of H929 cells and promote the apoptosis. Synergistic effects are found in combination with curcumin and bortezomib. Inhibition of nuclear factor NF-κB transcription and affect its regulation of apoptosis-related genes may be one of the mechanisms of action.