目的 探讨小檗胺选择性诱导FMS样酪氨酸激酶3（FMS-like tyrosine kinase 3，FLT3）基因突变急性白血病细胞凋亡及其可能作用机制。方法 应用MTT法比较小檗胺对FLT3突变阳性急性髓系白血病细胞株MV4-11和野生型FLT3肿瘤细胞胰腺癌细胞株PANC-1、淋巴瘤细胞株Pfeiffer、肺癌细胞株A549增殖的影响；流式细胞术检测小檗胺处理MV4-11后细胞凋亡和细胞周期的变化；Western blotting法检测FLT3及下游信号分子磷酸化STAT5（p-STAT5）蛋白的变化。结果 MTT结果显示，小檗胺作用于MV4-11细胞24、48、72 h的半数抑制浓度（IC₅₀）值分别是（7.039±0.700）、（4.840±0.271）、（2.088±0.376）μmol/L，明显低于野生型FLT3肿瘤细胞株；小檗胺作用于MV4-11细胞48 h后，随着小檗胺浓度增加，凋亡细胞比例增高，细胞周期停滞在G₀/G₁期。小檗胺呈浓度依赖性下调FLT3突变蛋白和p-STAT5蛋白的表达。结论 小檗胺能选择性下调FLT3突变蛋白及其下游信号分子p-STAT5，诱导FLT3突变急性髓系白血病MV4-11细胞凋亡和生长抑制。

Objective To investigate whether berbamine (BBM) can induce FMS-like tyrosine kinase 3 (FLT3) acute myeloid leukemia cells apoptosis selectively and its possible mechanism. Methods The growth inhibitory activities of BBM were evaluated between acute myeloid leukemia cells with FLT3 mutant and other cell lines without FLT3 mutant by MTT assay. Apoptotic rate and cell cycle were analyzed by flow cytometry. The related proteins of FLT3 pathway and the apoptosis associated proteins expression were measured by Western blotting. Results The growth of MV4-11 with BBM was inhibited significantly in a dose and time dependent manner with IC₅₀ (7.039 ±0.700), (4.840 ±0.271), and (2.088 ±0.376) μmol/L at 24, 48, and 72 h, respectively. Meanwhile, the apoptotic rate was increased dose-dependently, cell cycle arrested in G₀/G₁ phase. Furthermore, phosphorylation of STAT5, which was the downstream signaling of FLT3, was significantly reduced by BBM in a dose-dependent manner. Conclusion BBM can induce apoptosis in MV4-11 cells by the inhibition of FLT3 and downstream P-STAT5 signal pathway.

国家自然科学基金面上项目（30873095）；浙江省自然科学基金青年项目（LQ13H280004）