FA-2-b-β对慢性髓系白血病原代细胞的增殖抑制作用及其相关机制  

Inhibitory Effects of Agaricus Blazei Murrill(FA-2-b-β)on Proliferation of Chronic Myeloid Leukemia Cells in vivo and Its Mechanism

作　　者：程明霞 于尚睿 汪湛东 白坤恬 王东萍[1] 李娟[1] 刘世栋 孙延庆[1,2] 董莉 CHENG Ming-Xia;YU Shang-Rui;WANG Zhan-Dong;BAI Kun-Tian;WANG Dong-Ping;LI Juan;LIU Shi-Dong;SUN Yan-Qing;DONG Li(Department of Hematology,Gansu Provincial People′s Hospital,Lanzhou 730000,Gansu Province,China;Department of Clinical Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China;Department of Digestion,The Second Hospital of Lanzhou University,Lanzhou 730000,Gansu Province,China;Department of Cardiovascular Surgery,The First Hospital of Lanzhou University,Lanzhou 730000,Gansu Province,China)

机构地区：[1]甘肃省人民医院血液内科,甘肃兰州730000 [2]甘肃中医药大学,甘肃兰州730000 [3]兰州大学第二医院消化科,甘肃兰州730000 [4]兰州大学第一医院心血管外科,甘肃兰州730000

出　　处：《中国实验血液学杂志》2020年第6期1885-1891,共7页Journal of Experimental Hematology

摘　　要：目的:探讨秦巴硒菇提取物酸性RNA蛋白复合物(FA-2-b-β)抗慢性髓系白血病的效果及机制。方法:应用CCK-8法检测不同浓度FA-2-b-β对初诊慢性髓系白血病患者原代细胞增殖抑制作用;通过尾静脉注射原代白血病细胞建立慢性髓系白血病小鼠模型,观察模型小鼠生存期、血细胞数、体重变化;采用免疫荧光、免疫组织化学法、RT-qPCR及Western blot法检测caspase3信号通路相关凋亡基因和蛋白的表达。结果:体外实验显示,各药物浓度组中原代细胞增殖抑制率升高,且呈浓度时间依赖性(r24=0.9082,r48=0.9442,r72=0.9546)。组间比较差异具有统计学意义。体内实验显示,实验组(FA-2-b-β)和阳性对照组(伊马替尼)模型小鼠生存期均延长,并且血细胞数升高及体重恢复至正常,尽管白细胞数仍高;BAX、Caspase-3基因和蛋白表达上调,BCL-2、Cytochrome C、caspase 8、caspase 9、BCL/ABL基因和蛋白表达下降。结论:FA-2-b-β诱导慢性髓系白血病原代细胞凋亡,可延长慢性髓系白血病模型小鼠的生存期,其机制可能与caspase-3信号通路相关凋亡基因和蛋白有关。Objective:To investigated the anti-tumor in vivo effect and mechanism of the acid RNA protein complex(FA-2-b-β)of Agaricus blazei Murrill extract.Methods:CCK-8 method was used to detected the inhibitory effect of FA-2-b-βon proliferation of primary CML cells from newly diagnosed CML patients,the CML mouse model was established by trail-venous injection of primary CML cells,and the survival time,blood cell count and body weight were observed,the immunoflouresence and immunehistochemistry analysis,RT-qPCR,Western bolt were used to detemine the expression of caspase-3 signal pathway-related apoptosis genes and proteins.Results:The experiments in vitro showed that the proliferative inhibitory rate in drug-treated group increased with concentration-and time-dependent manner(r24=0.9092,r48=0.9442,r72=0.9546),the inter group comparison showed the statistical difference of results.The experiments in vitro showed that the survival time prolonged,blood cell count increased and body weight recovered in FA-2-b-β-treated group and imatinib-treated group,despite the WBC count is still high.The RT-qPCR and Western blot showed that the expression of BAX and caspase-3 gene and protein were up-regulated,the expression of BCL-2,cytochroime C,caspase-8,caspase-9 and BCL-ABL gene and protein were down-regulated.Conclusion:The FA-2-b-βcan induce apoptosis of primary CML cells and prolong the survival time of CML model mouse,which may be related with the caspase-3 signal pathway related genes and proteins.

关 键 词：秦巴硒菇 FA-2-b-β 伊马替尼 慢性髓系白血病 caspase3信号通路 

分 类 号：R733[医药卫生—肿瘤] R28[医药卫生—临床医学]