Duan Yong-Juan, Liu Chao, Chen Xiao-Yan, Wu Wen-Qi, Zheng Jia-Rui, Zhang Ying-Chi, Zhu Xiao-Fan
Pediatric Leukemia Diagnosis and Treatment Center, Institute of Hematology and Blood Disease Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
Tianjin Medical University, Tianjin 300070, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Jun;28(3):724-730. doi: 10.19746/j.cnki.issn.1009-2137.2020.03.002.
To study the effect of apoptotic drug Navitoclax (NTX) combined with chemotherapy drug Daunorubicin (DNR) on apoptosis of erythroleukemia cells.
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.
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).
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.
研究凋亡药物维托克洛司（NTX）联合化疗药物柔红霉素（DNR）对红白血病细胞凋亡的影响。
对数生长期的K562、HEL和TF-1细胞分别用NTX、DNR及两种药物联合处理。采用CCK-8检测、Annexin V-DAPI双染流式细胞术、实时RT-PCR分别检测细胞生长、细胞凋亡及BAX、BAK、BCL-2、BCL-xl和BIM的表达。比较分析NTX、DNR及两种药物联合对K562、HEL和TF-1细胞凋亡的影响。
NTX联合DNR可显著抑制K562、HEL和TF-1细胞的生长；凋亡检测结果显示，联合组K562、HEL和TF-1细胞的凋亡率显著高于NTX和DNR单药组；联合组K562细胞中凋亡相关基因BAK和BAX的表达水平显著高于两个单药组，抗凋亡蛋白基因BCL-2和BCL-xl的表达水平显著低于两个单药组（P＜0.05）；联合用药24小时处理的HEL细胞中BAK的表达水平高于DNR组（P＜0.05）；联合用药24小时处理的TF-1细胞中BCL-2的表达水平低于两个单药组，而联合用药48小时时BAK的表达水平在联合组中最高，联合组中BCL-2和BCL-xl的表达水平低于NTX组（P＜0.05）。
NTX联合DNR可显著促进红白血病细胞系K562、HEL和TF-1的凋亡，并诱导凋亡相关基因的表达。本研究为红白血病的临床治疗提供了新方案。
