【摘要】 目的:探讨紫杉醇对FLT3-ITD突变阳性急性髓系白血病(AML)细胞株MOLM-13增殖与凋亡的影响及可能机制。方法:选用紫杉醇(0～20 nmol/L)作用于MOLM-13细胞,CCK8法检测药物对细胞的增殖抑制作用,流式细胞术检测细胞凋亡率,实时荧光定量PCR(qPCR)法检测FLT3、PI3K、AKT、mTOR mRNA表达水平,Western blotting法检测AKT、磷酸化(p-)AKT蛋白的表达水平。结果:紫杉醇对MOLM-13细胞具有明显的增殖抑制及凋亡诱导作用,作用24h、48 h、72 h的IC50分别为14.19 nmol/L、4.73 nmol/L、3.39 nmol/L,作用48 h的凋亡率最高可达(63.2±0.87)%,明显高于对照组(P<0.05);10 nmol/L、20 nmol/L紫杉醇可明显下调FLT3、PI3K、AKT、mTOR mRNA以及AKT、p-AKT蛋白的表达水平(均P<0.05)。结论:紫杉醇对FLT3-ITD突变阳性AML细胞MOLM-13具明显的增殖抑制及诱导凋亡作用,可能与下调FLT3的表达以及抑制PI3K/AKT/mTOR信号通路有关。更多还原

【Abstract】 Objective: To investigate the effects of paclitaxel on the proliferation and apoptosis of FLT3-ITD mutation positive acute myeloid leukemia cell line MOLM-13 and its possible mechanism. Methods: MOLM-13 cells were treated with paclitaxel(0-20 nmol/L), and the inhibitory effect of paclitaxel on the proliferation of cells was detected by CCK8 assay. Flow cytometry method was used to analyze the apoptosis rate. The mRNA expression levels of FLT3, PI3 K, AKT, mTORwere detected by qPCR, and the protein expression levels of AKT and pAKT were detected by western blotting. Results: Paclitaxel could significantly inhibit the proliferation and induce the apoptosis of MOLM-13 cells, the IC50 of paclitaxel at 24 h, 48 h and 72 h were 14.19 nmol/L, 4.73 nmol/L, and 3.39 nmol/L, respectively. The apoptosis rate was up to(63.2 ± 0.87)% at 48 h, which was significantly higher than the control group(P<0.05). Paclitaxel could also down-regulate the expressions of FLT3, PI3 K,AKT, mTOR mRNA and AKT, p-AKT protein(P<0.05). Conclusion: Paclitaxel could significantly inhibit proliferation and induce apoptosis of FLT3-ITD mutation positive acute myeloid leukemia cell line MOLM-13,which may be related to down-regulate the FLT3 expression and inhibit the PI3 K/Akt/mTOR signaling pathway.更多还原