微残清颗粒逆转白血病干细胞耐药的机制研究  

Study on the Mechanism of Reversing Drug Resistance of Leukemia Stem Cells by WeiCanQing Granule

作　　者：闫理想 姜静 冯全管 杨向东[1] 何敬[1] 杨曦[1] 李德冠[4] 史哲新[1] YAN Lixiang;JIANG Jing;FENG Quanguan;YANG Xiangdong;HE Jing;YANG Xi;LI Deguan;SHI Zhexin(National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300381,China;Tianjin Academy of Traditional Chinese Medicine Afiliated Hospital,Tianjin 300120,China;Shanxi Provincial Integrated TCM and WM Hospital,Taiyuan 030002,China;Institute of Radiation Medicine,China Medical Academy of Sciences,Tianjin 300193,China)

机构地区：[1]天津中医药大学第一附属医院、国家中医针灸临床医学研究中心,天津300381 [2]天津市中医药研究院附属医院,天津300120 [3]山西省中西医结合医院,山西太原030002 [4]中国医学科学院放射医学研究所,天津300193

出　　处：《山西大学学报（自然科学版）》2024年第1期238-247,共10页Journal of Shanxi University(Natural Science Edition)

基　　金：天津中医药大学第一附属医院“拓新工程”基金项目(院2020057);天津市教委科研计划项目(2021KJ145);天津市科技计划项目(21JCQNJC01210)。

摘　　要：本文探讨了微残清颗粒在逆转白血病干细胞对柔红霉素(DNR)耐药中的作用机制。采用微残清颗粒兔含药血清干预CD34^(+)CD38^(-)KG1a白血病干细胞的方法,将免疫磁珠分选后的CD34^(+)CD38^(-)KG1a细胞分为对照组、DNR组、微残清颗粒组、微残清颗粒+DNR组,并应用siRNA法沉默磷酸酯酶与张力蛋白同源物(PTEN)表达,检测各组细胞增殖率、细胞周期/凋亡比例、胞内磷脂酰肌醇激酶(PI3K)/磷酸化蛋白激酶B(p-AKT)/磷酸化雷帕霉素靶蛋白(p-mTOR)mRNA及蛋白量。结果显示,微残清颗粒含药血清联合DNR可明显提高CD34^(+)CD38^(-)KG1a细胞的增殖抑制率、G2/M期比例、总凋亡和早期凋亡率。同时,微残清颗粒含药血清协同DNR提高PTEN mRNA及蛋白表达,降低PI3K、p-AKT、p-m TOR mRNA及蛋白表达。以上结果提示微残清颗粒具有逆转LSCs对DNR耐药的作用,作用机制可能与PTEN负调控PI3K/AKT/mTOR通路相关。This study explores the mechanism of action of WeiCanQing granule in reversing the resistance of leukemia stem cells to daunorubicin(DNR).Using the method of intervening CD34^(+)CD38^(-)KGla leukemia stem cells with rabbit serum containing Wei-CanQing granule,CD34^(+)CD38^(-)KGla cells sorted by immunomagnetic beads were divided into control group,DNR group,WeiCan-Qing granule group,and WeiCanQing granule+DNR group.Phosphatase and tensin homolog(PTEN)expression was silenced using siRNA method,and cell proliferation rate,cell cycle/apoptosis ratio,and Intracellular phosphatidylinositol kinase(PI3K)/phosphorylated protein kinase B(p-AKT)/phosphorylated rapamycin target protein(p-mTOR)mRNA and protein levels were examined.The results showed that the combination of WeiCanQing granule containing serum and DNR significantly increased the proliferation inhibition rate,G2/M phase ratio,total apoptosis,and early apoptosis rate of CD34^(+)CD38^(-)KGla cells.At the same time,the drug containing serum of WeiCanQing granule synergistically enhanced the expression of PTEN mRNA and protein,and reduces the expression of PI3K,p-AKT,p-mTOR mRNA and protein.The above results suggest that WeiCanQing granule have the effect of reversing LSCs'resistance to DNR,and the mechanism of action may be related to negative regulation of PTEN on the PI3K/AKT/mTOR pathway.

关 键 词：微残清颗粒 白血病干细胞 耐药 PTEN PI3K/AKT/mTOR通路 

分 类 号：R733.71[医药卫生—肿瘤]