目的 探讨isoangustone A调控人非小细胞肺癌A549细胞增殖及凋亡的分子机制。方法 将人肺癌细胞A549、H1299进行体外培养，用不同浓度（0.00、1.25、2.50、5.00、10.00、20.00 μmol/L）的isoangustone A干预细胞，分别处理36、72 h后，采用结晶紫染色法检测细胞增殖能力。以A549为细胞模型，通过流式细胞技术检测细胞的凋亡情况；经蛋白免疫印迹法检测凋亡相关蛋白及磷脂酰肌醇激酶（PI3K）/蛋白激酶B（Akt）、c-Jun氨基末端激酶（JNK）/p38丝裂原活化蛋白激酶（p38 MAPK）信号通路的表达。结果 与对照组比较，随着isoangustone A浓度的增加和处理时间的延长，A549、H1299细胞增殖能力逐渐降低（P＜0.05、0.01、0.001），呈浓度和时间相关性。经10.00 μmol/Lisoangustone A处理后，A549细胞凋亡率显著升高（P＜0.01）；isoangustone A 2.50、5.00、10.00 μmol/L组A549细胞p-Akt/Akt蛋白水平显著降低（P＜0.01）；isoangustone A 5.00、10.00μmol/L组B淋巴细胞瘤-2（Bcl-2）/Bcl-2相关X蛋白（Bax）、p-PI3K/PI3K的表达水平显著降低（P＜0.05）；半胱氨酸蛋白酶-8（Caspase-8）、cleaved-Caspase-3、p-p38/p38的表达水平显著增加（P＜0.05、0.001）；经10.00 μmol/Lisoangustone A处理后，cleaved-多聚腺苷二磷酸核糖聚合酶（PARP）和p-JNK/JNK的表达显著升高（P＜0.05、0.01）。结论 isoangustone A可抑制肺癌A549细胞的增殖，并诱导其发生凋亡，其作用机制可能与调控PI3K/Akt及JNK/p38 MAPK信号通路有关。

Objective To investigate the molecular mechanism of isoangustone A on proliferation and apoptosis of human non-small cell lung cancer A549 cells. Methods A549 and H1299 cells were cultured in vitro and treated with different concentrations (0.00, 1.25, 2.50, 5.00, 10.00, 20.00 μmol/L) of isoangustone A for 36 and 72 h, respectively. The proliferation inhibition rate of A549 and H1299 cells were detected by crystal violet staining. Using A549 cell as a model, apoptosis was detected by flow cytometry, Western blotting was used to detect the expression of PI3K/Akt and JNK/p38 MAPK signaling pathways as well as apoptosis-related proteins in each group. Results Compared with control group, after treatment with different concentrations of isoangustone A for 36 and 72 h, the proliferation of A549 and H1299 cells was inhibited (P < 0.05, 0.01, 0.001), and showed concentration-dependent and time-dependent. The apoptosis rate of A549 cells in the 10.00 μmol/L isoangustone A group was significantly increased (P < 0.01). The p-Akt/Akt protein level in isoangustone A (2.50, 5.00, 10.00 μmol/L) groups were significantly reduced (P < 0.01). The expression of Bcl-2/Bax and p-PI3K/PI3K in the isoangustone A (5.00, 10.00 μmol/L) groups were significantly reduced (P < 0.05), and the expression of cleaved-Caspase 3, Caspase 8, and p-p38/p38 were significantly increased (P < 0.05, 0.001). The levels of 10.00 μmol/Lof isoangustone A was able to upregulate the levels of cleaved-PARP and p-JNK/JNK (P < 0.05, 0.01). Conclusion Isoangustone A can inhibit the proliferation and promote apoptosis of A549 cells, which may be related to the regulation of PI3K/Akt and JNK/p38 MAPK signaling pathways.

R966;R979.1

贵州省科技计划项目（黔科合支撑[2020]4Y118号）；广东省基础与应用基础研究基金资助项目（粤基金字[2021]24号）；毕节市科学技术计划项目（毕科联合字sy[2022]11号）；佛山市自筹经费类科技创新项目（2320001006394）；佛山市“十四五”医学重点专科和培训专科项目（FSZD145035）