【摘要】 目的：研究紫杉醇（PTX）对FLT3-ITD突变急性髓细胞白血病细胞株MOLM-13增殖与凋亡的影响及作用机制。方法：不同浓度的PTX分别作用于FLT3-ITD突变细胞MOLM-13和FLT3未突变细胞THP-1, 采用CCK8法及流式细胞仪FITC/PI双标法分别检测PTX对两种细胞株增殖与凋亡的影响；采用实时荧光定量PCR法（RT-qPCR）及western blotting法分别检测PTX对 MOLM-13 细胞株 FLT3、NF-κB 基因及蛋白表达的影响。结果：PTX 作用于 MOLM-13 细胞 24 h、48 h、72 h 的 IC₅₀分别为7.659 nmol/L、3.748 nmol/L、3.408 nmol/L，而 THP-1 细胞的 IC₅₀为 61.164 nmol/L、11.804 nmol/L、9.834 nmol/L。4 nmol/L 和8 nmol/L PTX 作用 MOLM-13 细胞 48 h 的凋亡率分别为（13.12±0.20）%、（46.27±1.48）%，与对照组[（9.95±0.48）%]相比凋亡率升高（P<0.05）;4 nmol/L和8 nmol/L PTX作用THP-1细胞48 h后的凋亡率分别为（4.26±2.06）%、（8.22±0.47）%,8 nmol/L PTX处理组凋亡率比对照组[（5.26±0.83）%]高（P<0.05）。经 PTX 处理 48 h 后，MOLM-13 细胞中 FLT3、NF-κB 基因表达下调，FLT3、NF-κB、p-NF-κB 蛋白表达下调（P<0.05）。结论：与 FLT3 未突变白血病细胞株 THP-1 相比，PTX 对 FLT3-ITD 突变细胞株MOLM-13的抑制作用更为明显，且呈剂量和时间依赖性；PTX对MOLM-13细胞的作用机制可能与下调FLT3、NF-κB以及p-NF-κB 蛋白的表达，进而诱导白血病细胞发生凋亡有关。更多还原

【Abstract】 Objective: To study the effects of paclitaxel （PTX） on the proliferation and apoptosis of FLT3-ITD mutant acute myeloid leukemia cell line MOLM- 13 and its mechanism. Methods: Different concentrations of PTX were applied to FLT3-ITD mutant cells MOLM-13 and FLT3 mutation-free cells THP-1, and the effects of PTX on the proliferation and apoptosis of the two cell lines were detected by CCK8 assay and flow cytometry FITC/PI double- labeling. The effects of PTX on the mRNA and protein expressions of FLT3 and NF- κB in MOLM-13 cells were detected by RT-qPCR and western blotting. Results: The IC₅₀of PTX acting on MOLM-13cells at 24 h, 48 h and 72 h were 7.659 nmol/L, 3.748 nmol/L and 3.408 nmol/L respectively, while the IC₅₀of THP-1 cells were 61.164 nmol/L, 11.804 nmol/L and 9.834 nmol/L respectively. The apoptosis rates of 4 nmol/L and 8 nmol/L PTX-treated MOLM-13 cells at 48 h were （13.12±0.20）% and （46.27±1.48）% respectively, and the apoptosis rates were increased compared with the control group [（9.95±0.48）%, P<0.05]. The apoptosis rates of 4 nmol/L and 8 nmol/L PTX- treated THP-1 cells at 48 h were （4.26±2.06）% and （8.22±0.47）% respectively, and the apoptosis rate was significantly higher in the 8 nmol/L PTX-treated group compared with the control group [（5.26±0.83）%, P<0.05].After 48 h of PTX treatment, the mRNA expressions of FLT3 and NF- κB were down- regulated in MOLM- 13cells （P<0.05）. FLT3, NF-κB and p-NF-κB protein expressions were lower in MOLM-13 cells than those in the control group after 48 h of PTX treatment （P<0.05）. Conclusion: Compared with the FLT3 mutation-free leukemia cell line THP- 1, the inhibitory effect of PTX on the FLT3- ITD mutant cell line MOLM- 13 is more pronounced and dose- and time-dependent; the mechanism of PTX acting on MOLM-13 cells may be related to the down-regulation of FLT3, NF-κB, and p-NF-κB protein expressions, which in turn is associated with the induction of leukemia cell apoptosis.更多还原