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(Li2CO3)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Li2CO3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Li2CO3，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Li2CO3浓度下存活率不同(P＜0。01)。Li2CO3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，Li2CO3 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、Li2CO3组、VCR组和Li2CO3联合VCR组，2种细胞Li2CO3联合VCR组的G2/M期和凋亡细胞占比最高，Li2CO3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，Li2CO3与VCR联合促进T-ALL细胞增殖抑制，使细胞周期阻滞于G2/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。
Lithium Carbonate Combined with Vincristine Inhibits the Proliferation and Promotes Apoptosis of Children's Acute T Lymphoblastic Leukemia Cells
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 chemo-therapy drug for children with significant efficacy in T-ALL,but its side effects are obvious.Lithium car-bonate(Li2CO3)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 Li2CO3 com-bined 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 Li2CO3 alone,which compared with the control group(P＜0.05).The survival rates of the two kinds of cells were dif-ferent under the same Li2CO3 concentration(P＜0.01).Compared with the VCR group,the cell viability and half maximal inhibitory concentration(ICso)values of Li2CO3 combined with VCR group were re-duced in the two kinds of cells,and the coefficient of drug interaction(CDI)between Li2CO3 and VCR was less than 1.Flow cytometry showed Li2CO3 combined with VCR group had the highest proportion of G2/M and apoptotic cells of the two kinds of cells among the control,Li2CO3,VCR and,Li2CO3 com-bined with VCR group.And there were significant differences between Li2CO3 combined with VCR group and VCR group(P＜0.05).In conclusion,our experimental results suggest that the combination of Li2CO3 and VCR inhibits of T-ALL cell proliferation,arrests the cell cycle in the G2/M phase and increa-ses 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.
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