6-姜辣素对人多发性骨髓瘤细胞的抑制作用及分子机制  

The inhibitory effect and molecular mechanism of 6-gingerol on human multiple myeloma cells

作　　者：孔春芳[1,2] 李安娜 柯波[1,2] 丁伟荣 刘婷婷[1,2] 符环 张婷婷[1,2] 金成豪 吴美[1,2] KONG Chunfang;LI Anna;KE Bo;DING Weirong;LIU Tingting;FU Huan;ZHANG Tingting;JIN Chenghao;WU Mei(Department of Hematology,Jiangxi Provincial People′s Hospital,the First Affiliated Hospital of Nanchang Medical College,Nanchang 330006,Jiangxi,China;Jiangxi Province Key Laboratory of Hematologic Diseases,Nanchang 330006,Jiangxi,China)

机构地区：[1]江西省人民医院(南昌医学院第一附属医院)血液内科,江西南昌330006 [2]江西省血液病重点实验室,江西南昌330006

出　　处：《实用医学杂志》2024年第23期3291-3297,共7页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81560026);江西省中医药管理局科技计划课题(编号:2022B783)。

摘　　要：目的研究6-姜辣素对人多发性骨髓瘤细胞的抑制作用及分子机制。方法体外培养人多发性骨髓瘤RPMI 8226、ARH77细胞,加入不同浓度(50、100、200、300、400μmol/L)的6-姜辣素处理RPMI 8226、ARH77细胞,CCK-8法测定细胞增殖抑制率;流式细胞术检测细胞凋亡和周期;qRT-PCR和Western blotting法检测基因和蛋白表达水平。结果6-姜辣素以剂量和时间依赖的方式抑制RPMI8226、ARH77细胞的增殖,并诱导其凋亡,差异有统计学意义(P<0.05);进一步机制研究发现6-姜辣素处理RPMI 8226细胞后,将细胞阻滞在G_(0)/G_(1)期,显著增加Bax mRNA水平,降低Bcl-2 mRNA和c-Myc mRNA的水平(P<0.05);同时显著增加Bax、Cleaved-PARP、Cleaved-caspase3、P53、p-AKT蛋白的表达,而降低Bcl-2蛋白的表达(P<0.05)。结论6-姜辣素可抑制MM细胞增殖及诱导其凋亡,并阻滞细胞周期在G_(0)/G_(1)期,其机制可能与抑制AKT信号通路并通过影响Bcl-2家族蛋白表达以及c-Myc表达受抑等密切有关。Objective To investigate the inhibitory effect and elucidate the molecular mechanism of 6⁃gingerol on human multiple myeloma cells.Methods The human multiple myeloma cell lines RPMI 8226 and ARH77 were cultured in vitro,followed by treatment with varying concentrations(50,100,200,300,400μmol/L)of 6⁃gingerol.The inhibitory effect on cell proliferation was assessed using the CCK⁃8 assay.Flow cytometry was employed to evaluate cell apoptosis and cycle distribution.Additionally,qRT⁃PCR and Western blotting techniques were utilized to analyze gene and protein expression levels.Results The proliferation of RPMI 8226 and ARH77 cells was dose⁃and time⁃dependently inhibited by 6⁃gingerol,leading to the induction of apoptosis with statistically significant differences(P<0.05).Further mechanistic investigations revealed that treatment with 6⁃gingerol arrested RPMI 8226 cells in the G_(0)/G_(1)phase,resulting in a significant increase in Bax levels and a decrease in Bcl⁃2 mRNA and c⁃Myc mRNA levels(P<0.05).Additionally,it significantly upregulated the expression of Bax,Cleaved⁃PARP,Cleaved⁃caspase3,P53,and p⁃AKT proteins while down regulating the expression of Bcl⁃2 protein(P<0.05).Conclusions The compound 6⁃Gingerol exhibits inhibitory effects on the proliferation and induction of apoptosis in MM cells,as well as cell cycle arrest at the G_(0)/G_(1)phase.Its mechanism of action is likely associated with the suppression of the AKT signaling pathway,downregulation of Bcl⁃2 family protein expression,and inhibition of c⁃Myc expression.

关 键 词：多发性骨髓瘤 6-姜辣素 细胞增殖 细胞凋亡 信号通路 

分 类 号：R559[医药卫生—血液循环系统疾病]