摘要
儿童急性T淋巴细胞白血病(T-cell acute lymphoblastic leukemia,T-ALL)是T系前体细胞发生恶性转化的一种侵袭性肿瘤,化疗药物的毒副作用及耐药性问题仍然是阻碍其治疗成功的难题。长春新碱(vincristine,VCR)是治疗儿童T-ALL疗效显著的传统化疗药物,但其副作用明显。碳酸锂(Li_(2)CO_(3))可增强其它化疗药物的疗效,但其联合VCR的研究未见报道。该研究旨在探讨Li_(2)CO_(3)联合VCR对2种儿童T-ALL细胞系CCRF-CEM和Jurkat细胞增殖、凋亡及细胞周期的作用。噻唑蓝(thiazolyl blue tetrazolium bromide,MTT)比色法结果显示,与对照组比较,单用VCR或Li_(2)CO_(3),随着其浓度的增加,2种细胞存活率均逐渐降低(P<0.05)。2种细胞在相同Li_(2)CO_(3)浓度下存活率不同(P<0.01)。Li_(2)CO_(3)联合VCR处理细胞存活率与单独VCR组处理相比,2种细胞的细胞存活率和VCR的半抑制浓度(half maximal inhibitory concentration,IC_(50))值降低,Li_(2)CO_(3)与VCR的2药相互作用指数(coefficient of drug interaction,CDI)均小于1。流式细胞仪检测结果发现,对照组、Li_(2)CO_(3)组、VCR组和Li_(2)CO_(3)联合VCR组,2种细胞Li_(2)CO_(3)联合VCR组的G_(2)/M期和凋亡细胞占比最高,Li_(2)CO_(3)联合VCR组和VCR组比,均存在显著性差异(P<0.05)。总之,我们的研究结果提示,Li_(2)CO_(3)与VCR联合促进T-ALL细胞增殖抑制,使细胞周期阻滞于G_(2)/M期,且促进细胞凋亡,结果为儿童T-ALL临床治疗及减少VCR毒副作用提供了新的实验依据,也为其药物研发提供新的思路。
T-cell acute lymphoblastic leukemia(T-ALL)is an aggressive tumor,in which T precursor cells undergo malignant transformation,and the side effects and drug resistance of chemotherapy drugs are still difficult problems hindering the success of treatment.Vincristine(VCR)is a traditional chemotherapy drug for children with significant efficacy in T-ALL,but its side effects are obvious.Lithium carbonate(Li_(2)CO_(3))can enhance the efficacy of other chemotherapy drugs,but studies of its combination with VCR have not been reported.The purpose of this study is to investigate the effects of Li_(2)CO_(3) combined with VCR on the proliferation,apoptosis and cell cycle of two pediatric T-ALL cell lines,CCRF-CEM and Jurkat cells.The results of thiazolyl blue tetrazolium bromide(MTT)colorimetric assay showed that the viability of both cells decreased with the increase of the concentration of VCR or Li_(2)CO_(3) alone,which compared with the control group(P<0.05).The survival rates of the two kinds of cells were different under the same Li_(2)CO_(3) concentration(P<0.01).Compared with the VCR group,the cell viability and half maximal inhibitory concentration(IC_(50))values of Li_(2)CO_(3) combined with VCR group were reduced in the two kinds of cells,and the coefficient of drug interaction(CDI)between Li_(2)CO_(3) and VCR was less than 1.Flow cytometry showed Li_(2)CO_(3) combined with VCR group had the highest proportion of G_(2)/M and apoptotic cells of the two kinds of cells among the control,Li_(2)CO_(3),VCR and,Li_(2)CO_(3) combined with VCR group.And there were significant differences between Li_(2)CO_(3) combined with VCR group and VCR group(P<0.05).In conclusion,our experimental results suggest that the combination of Li_(2)CO_(3) and VCR inhibits of T-ALL cell proliferation,arrests the cell cycle in the G_(2)/M phase and increases cell apoptosis,which provides a new experimental basis for the clinical treatment of pediatric T-ALL,the reduction of VCR side effects,and also new ideas for drug development.
作者
张祚
杨爱云
路媛芳
肖志轩
王建华
赵丽娇
ZHANG Zuo;YANG Ai-Yun;LU Yuan-Fang;XIAO Zhi-Xuan;WANG Jian-Hua;ZHAO Li-Jiao(Beijing Key Laboratory of Environmental and Viral Oncology,Faculty of Environment and Life Sciences,Beijing University of Technology,Beijing 100124,China;Beijing Key Laboratory of Child Development Nutriomics,Translational Medicine Laboratory,Capital Institute of Pediatrics,Beijing 100020,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2024年第5期647-655,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
首都儿科研究所所级课题(No.JCYJ-2023-15)
首都儿科研究所创新工程专项(No.CXYJ-2021-03)
北京市自然科学基金(No.7222016)资助。
关键词
白血病
碳酸锂
长春新碱
增殖
凋亡
leukemia
lithium carbonate
vincristine(VCR)
proliferation
apoptosis
