摘　要：基于磷脂酰肌醇3-激酶（PI3K）/丝苏氨酸蛋白激酶（AKT）信号通路探究安罗替尼对A549细胞增殖、凋亡的影响。将A549细胞分为对照组、各剂量试验组、安罗替尼组、阳性药物组、抑制剂组和激活剂组。干预24 h后检测A549细胞活力、细胞形态、增殖率、凋亡情况及相关蛋白的表达水平。结果显示：20 μmol/L安罗替尼处理后，A549细胞活力降低；安罗替尼组和阳性药物组较对照组A549细胞生长受到抑制，细胞增殖率、细胞周期素D1（Cyclin D1）及p-PI3K、p-AKT的表达水平降低，细胞凋亡数量和半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）的表达水平升高。抑制剂增强了上述各指标的变化，而激活剂则具有与抑制剂相反的趋势。该研究结果说明，安罗替尼可显著抑制人肺癌A549细胞的增殖并促进其凋亡，其作用机制可能与抑制PI3K/AKT通路的信号转导相关。该研究结果进一步说明了安罗替尼作为抗肺癌药物的潜在价值，为抗肺癌药物的研发提供了新的理论基础。
关键词：安罗替尼；肺癌；激酶信号通路；增殖；凋亡
中图分类号：R734.2                             文献标志码：A                DOI：10.3969/j.issn.1007-7146.2023.04.009

Abstract: To investigate the effects of anlotinib on proliferation and apoptosis of A549 cells based on phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT) signaling pathway. A549 cells were divided into the control group, the experimental groups with different doses, the anlotinib group, the positive drug group, the inhibitor group and the activator group. The intervention time was 24 hours. The cell viability, cell morphology, the rate of proliferation, apoptosis and related protein expression levels were detected. The results showed that cell viability decreased after treatment with 20 μmol/L anlotinib. Compared with the control group, the cell growth of anlotinib group and positive drug group was inhibited, the cell proliferation rate, cysteinyl aspartate specific proteinase D1 (Cyclin D1)  and the expression levels of p-PI3K and p-AKT decreased, and the number of apoptosis cells and the expression of cysteine aspartic protease-3 (Caspase-3) increased. The inhibitor enhanced these changes, while the activator had the opposite trend to the inhibitor. These results of this study indicate that anlotinib can significantly inhibit the proliferation and promote apoptosis of A549 cells, and its mechanism might be related to the inhibition of PI3K/AKT pathway signal transduction. The results of this study further illustrate the potential value of antilung cancer drugs and provide a new theoretical basis for the research and development of anti-lung cancer drugs.
Key words: anlotinib; lung cancer; kinase signaling pathway; proliferation; apoptosis
（Acta Laser Biology Sinica, 2023, 32(4): 360-367）