目的 探討isoangustone A調(diào)控人非小細(xì)胞肺癌A549細(xì)胞增殖及凋亡的分子機制。方法 將人肺癌細(xì)胞A549、H1299進行體外培養(yǎng)，用不同濃度（0.00、1.25、2.50、5.00、10.00、20.00 μmol/L）的isoangustone A干預(yù)細(xì)胞，分別處理36、72 h后，采用結(jié)晶紫染色法檢測細(xì)胞增殖能力。以A549為細(xì)胞模型，通過流式細(xì)胞技術(shù)檢測細(xì)胞的凋亡情況；經(jīng)蛋白免疫印跡法檢測凋亡相關(guān)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絲裂原活化蛋白激酶（p38 MAPK）信號通路的表達。結(jié)果 與對照組比較，隨著isoangustone A濃度的增加和處理時間的延長，A549、H1299細(xì)胞增殖能力逐漸降低（P＜0.05、0.01、0.001），呈濃度和時間相關(guān)性。經(jīng)10.00 μmol/Lisoangustone A處理后，A549細(xì)胞凋亡率顯著升高（P＜0.01）；isoangustone A 2.50、5.00、10.00 μmol/L組A549細(xì)胞p-Akt/Akt蛋白水平顯著降低（P＜0.01）；isoangustone A 5.00、10.00μmol/L組B淋巴細(xì)胞瘤-2（Bcl-2）/Bcl-2相關(guān)X蛋白（Bax）、p-PI3K/PI3K的表達水平顯著降低（P＜0.05）；半胱氨酸蛋白酶-8（Caspase-8）、cleaved-Caspase-3、p-p38/p38的表達水平顯著增加（P＜0.05、0.001）；經(jīng)10.00 μmol/Lisoangustone A處理后，cleaved-多聚腺苷二磷酸核糖聚合酶（PARP）和p-JNK/JNK的表達顯著升高（P＜0.05、0.01）。結(jié)論 isoangustone A可抑制肺癌A549細(xì)胞的增殖，并誘導(dǎo)其發(fā)生凋亡，其作用機制可能與調(diào)控PI3K/Akt及JNK/p38 MAPK信號通路有關(guān)。

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

貴州省科技計劃項目（黔科合支撐[2020]4Y118號）；廣東省基礎(chǔ)與應(yīng)用基礎(chǔ)研究基金資助項目（粵基金字[2021]24號）；畢節(jié)市科學(xué)技術(shù)計劃項目（畢科聯(lián)合字sy[2022]11號）；佛山市自籌經(jīng)費類科技創(chuàng)新項目（2320001006394）；佛山市“十四五”醫(yī)學(xué)重點?？坪团嘤?xùn)?？祈椖浚‵SZD145035）