摘要
目的:探讨茅莓总皂苷(TSRP)逆转慢性粒细胞白血病(CML)伊马替尼(IM)耐药的作用机制。方法:采用极限梯度稀释法构建IM耐药细胞株K562R,将K562R细胞分为空白组(K562R细胞)、TSRP干预组(TSRP)、IM干预组(IM)、TSRP联合IM干预组(TSRP+IM)。采用CCK8法检测K562R细胞的增殖情况;流式细胞术检测K562R细胞的凋亡率;Western blot法检测PI3K/AKT信号通路相关蛋白的表达。结果:与空白组比较,TSRP+IM组K562R细胞的存活率显著降低(P<0.01),凋亡率显著升高(P<0.01);TSRP+IM组K562R细胞p-PI3K与p-AKT蛋白表达水平较空白组显著下降(P<0.01);与空白组比较,IM组细胞活性显著降低(P<0.05),与IM组比较,IM+TSRP组细胞活性显著降低(P<0.05)。结论:TSRP与IM具有协同效果,两者联合用药显著优于单药组,能抑制K562R细胞的增值,促进K562R细胞凋亡;TSRP可能是通过PI3K/AKT通路逆转CML的IM耐药。
Objective:To investigate the mechanism of total saponins of Rubus parvifolius L.(TSRP)in reversing Imatinib(IM)resistance in chronic myelogenous leukemia(CML).Methods:IM-resistant cell line K562R was constructed by limiting gradient dilution method,and K562R cells were divided into control group(K562R cells),TSRP intervention group(K562R cells+TSRP),IM intervention group(K562R cells+IM),and TSRP combined with IM intervention group(K562R cells+TSRP+IM).The proliferation of K562R cells was detected by CCK8 method.The apoptosis rate of K562R cells was detected by flow cytometry.The expressions of related proteins in PI3K/AKT signaling pathway were detected by Western blot.Results:Compared with control group,the survival rate of K562R cell in TSRP+IM group was significantly decreased(P<0.01),and the apoptosis rate was significantly increased(P<0.01).The expression levels of P-PI3K and P-Akt in K562R cells in TSRP+IM group were significantly decreased compared with those in control group(P<0.01).Compared with control group,the cell activity in IM group was significantly decreased(P<0.05),and that in IM+TSRP group was significantly decreased compared with IM group(P<0.05).Conclusion:TSRP and IM had a synergistic effect,and the effect of combination of TSRP and IM was significantly better than that of the single drug group,which could inhibit the proliferation of K562R cells and promote the apoptosis of K562R cells.The effects of TSRP may reverse IM resistance to CML through the PI3K/AKT pathway.
作者
程佳俊
许晓峰
叶杨
何潆
CHENG Jiajun;XU Xiaofeng;YE Yang;HE Ying(Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine,Hangzhou Red Cross Hospital,Hangzhou,Zhejiang 310003)
出处
《中国中医药科技》
2025年第6期964-969,共6页
Chinese Journal of Traditional Medical Science and Technology
基金
浙江省中医药科技计划项目(2021ZQ069)。