Objective: To study the effect of apoptotic drug Navitoclax (NTX) combined with chemotherapy drug Daunorubicin (DNR) on apoptosis of erythroleukemia cells.
Methods: K562, HEL and TF-1 cells in logarithmic growth phase were treated with NTX, DNR and combination of the two drugs. CCK-8 test, Annexin V-DAPI double-staining flow cytometry, real-time RT-PCR were used to detect cell growth, cell apoptosis and expression of BAX, BAK, BCL-2, BCL-xl and BIM respectively. The effects of NTX, DNR and combination of the two drugs on apoptosis of K562, HEL and TF-1 cells were compared and analyzed.
Results: NTX combined with DNR could significantly inhibit the growth of K562, HEL and TF-1 cells; Apoptosis detection results showed that the apoptotic rate of K562, HEL and TF-1 cells in combination group was significantly higher than that in NTX and DNR single group; the expression level of apoptosis-related genes BAK and BAX in K562 cells in combination group was significantly higher than that in two single drug groups, and the expression level of anti-apoptotic protein genes BCL-2 and BCL-xl was significantly lower than that in two single drug groups (P＜0.05); the expression level of BAK in HEL cells treated with combined drugs for 24 hours was higher than that in DNR group (P ＜ 0.05); the expression level of BCL-2 in TF-1 cells treated with combined drugs for 24 hours was lower than that in two single drugs groups while the expression level of BAK in 48 hours was the highest in combined drugs group, and the expression level of BCL-2 and BCL-xl in combined drugs group was lower than that in NTX group (P＜0.05).
Conclusion: NTX combined with DNR can significantly promote the apoptosis of erythroleukemia cell lines K562, HEL and TF-1, and induce the expression of apoptosis-related genes. This study provides a new scheme for the clinical treatment of erythroleukemia.
题目: Navitoclax联合柔红霉素促进红白血病细胞系K562、HEL和TF-1的凋亡.
目的: 研究促凋亡药物Navitoclax（NTX）联合化疗药物柔红霉素（Daunorubicin，DNR）对红白血病细胞凋亡的影响.
方法: 取对数生长期的K562、HEL和TF-1细胞，给予NTX、DNR以及2药联合，CCK-8检测细胞生长，Annexin V-DAPI双染流式细胞术检测细胞的凋亡，real-time RT-PCR检测凋亡相关基因BAX，BAK，BCL-2、BCL-xl、BIM的表达，对比分析NTX、DNR与2药联合对K562、HEL和TF-1细胞凋亡的影响.
结果: NTX联合DNR能明显抑制K562、HEL和TF-1细胞的生长；凋亡检测结果显示，联合用药组K562、HEL和TF-1细胞凋亡率明显高于NTX、DNR单用药组（P＜0.05）；凋亡相关基因检测结果显示，K562细胞前凋亡蛋白基因BAK、BAX的表达水平在联合用药组明显高于2个单药组,抗凋亡蛋白基因BCL-2、BCL-xl的表达水平明显低于2个单药组（P＜0.05）；HEL细胞联合用药24 h BAK的表达水平高于DNR单药组（P＜0.05）；TF-1细胞联合用药24 h BCL-2的表达低于2个单用药组，48 h BAK的表达联合用药组最高，BCL-2、BCL-xl的表达水平在联合用药组低于NTX单药组（P＜0.05）.
结论: NTX联合DNR能明显促进红白血病细胞系K562、HEL和TF-1细胞凋亡，诱导凋亡相关基因的表达。本研究期待为红白血病的临床治疗提供新方案.