目的 研究LZ-106对间变性淋巴瘤激酶（ALK）激酶活性的抑制作用，及对ALK阳性细胞的生长抑制作用。方法 采用分子对接模拟LZ-106与ALK的结合，通过体外激酶活性实验检测其对ALK激酶活性的影响，通过CCK-8实验检测其对H2228细胞的生长抑制作用，通过Annexin V/PI细胞凋亡实验检测其对H2228细胞的凋亡作用，通过Western blotting检测其对H2228细胞p-ALK及下游信号通路关键激酶表达的影响。结果 LZ-106能抑制ALK激酶活性，半数抑制浓度（IC₅₀）为（15.51±2.09）nmol/L，其能显著抑制H2228细胞存活率，并能浓度相关性地诱导细胞凋亡。Western blotting实验显示LZ-106可以显著抑制p-ALK、p-蛋白激酶B（Akt）及p-信号转导因子和转录激活因子3（STAT3）的表达，且Akt及STAT3激活剂可以明显削弱LZ-106的凋亡诱导作用。结论 LZ-106显著抑制ALK激酶活性，诱导ALK阳性细胞凋亡，激活Akt及STAT3可以逆转LZ-106所致的细胞凋亡。

Objective To study the inhibitory effect of LZ-106 on ALK activity and growth inhibition of ALK positive cells. Methods The binding of LZ-106 to ALK was simulated by molecular docking, its effect on ALK kinase activity was detected by in vitro kinase activity assay, its growth inhibition effect on H2228 cells was detected by CCK-8 assay, and its apoptosis effect on H2228 cells was detected by Annexin V/PI apoptosis assay. Western blotting was used to detect its effects on the expression of p-ALK and key kinases in the downstream signaling pathway of H2228 cells. Results LZ-106 can inhibit the activity of ALK kinase with IC₅₀ of 15.51 ± 2.09 nmol/L, which can significantly inhibit the survival rate of H2228 cells and induce cell apoptosis in a concentration-dependent manner. Western blotting experiments showed that LZ-106 could significantly inhibit the expression of p-ALK, p-Akt, and p-STAT3, and Akt and STAT3 activators could significantly weaken the apoptosis-inducing effect of LZ-106. Conclusion LZ-106 significantly inhibits ALK kinase activity and induces apoptosis of ALK-positive cells. Activation of Akt and STAT3 can reverse the apoptosis caused by LZ-106.

R966

江苏省自然科学基金资助项目（BK20151443），江苏省中医院院级课题（Y20038）