| 郭秋生,汤婉芬,周师师,郑志坚,吕仙梅.水仙环素通过调控PLK1/AKT信号通路诱导三阴性乳腺癌细胞细胞周期阻滞和凋亡[J].浙江中西医结合杂志,2024,34(2): |
| 水仙环素通过调控PLK1/AKT信号通路诱导三阴性乳腺癌细胞细胞周期阻滞和凋亡 |
| Narciclasine induces cell cycle arrest and apoptosis in triple negative breast cancer cells by regulating PLK1/AKT signal pathway |
| 投稿时间：2023-06-09 修订日期：2024-01-04 |
| DOI： |
| 中文关键词: 三阴性乳腺癌 水仙环素 凋亡 细胞周期 PLK1/AKT信号通路 |
| 英文关键词:TNBC Narciclasine apoptosis cell cycle PLK1/AKT signal pathway |
| 基金项目:金华市中心医院基础研究专项科研基金项目，基金号：JY2022-6-06。 |
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| 中文摘要: |
| 摘 要：目的 研究水仙环素（Narciclasine，Nas）对人三阴性乳腺癌（Triple negative breast cancer，TNBC）细胞周期和凋亡的抑制作用及分子机制。方法 采用细胞增殖-毒性检测试剂盒（Cell Counting Kit-8，CCK-8）、克隆形成、Transwell、流式细胞术等实验分析Nas对TNBC细胞株MDA-MB-231细胞增殖和侵袭能力的抑制作用，及对细胞周期和凋亡的诱导作用；利用免疫印迹（Western blot，WB）实验分析Nas对MDA-MB-231细胞株cle-Caspase-3、PARP、cle-PARP、PLK1、PI3K、p-PI3K、AKT、p-AKT、CDK1、Cyclin B、Cyclin A、p-21、p-27、p-62、LC3、γ-H2AX等蛋白质的影响。结果 不同浓度的Nas（浓度分别为0.5 μmol/L、1.0 μmol/L、2.0 μmol/L）能抑制MDA-MB-231细胞株的克隆形成（48 h抑制率分别为15.99%、24.76%和54.17%）、侵袭能力（48h抑制率分别为0.68%、23.20%和45.27%），可将细胞周期阻滞于G2期（48 h阻滞率分别为75.50%、140.56%和316.06%），可对细胞凋亡起到诱导作用（48 h凋亡诱导率分别为105.39%、199.73%和375.74%；72 h凋亡诱导率分别为104.45%、244.96%和709.60%）。分子机制实验显示Nas可以显著促进cle-Caspase-3、cle-PARP、γ-H2AX、p-21及p-27等蛋白质的表达，显著抑制PLK1、p-PI3K、p-AKT、CDK1、Cyclin B等蛋白质的表达水平，而对PARP、p-62、LC3-II/I、PI3K、Cyclin A等蛋白质的表达水平影响不明显。结 论 Nas能抑制MDA-MB-231细胞株的克隆形成、侵袭能力，对凋亡起到诱导作用，并将细胞周期阻滞于G2期，该机制可能通过调节PLK1/AKT信号通路来实现。 |
| 英文摘要: |
| ABSTRACT:Objective To investigate the inhibitory effect and molecular mechanism of Narciclasine (Nas) on cell cycle and apoptosis in human triple negative breast cancer (TNBC) cells.Methods CCK-8, clone formation, transwell and flow cytometry were used to analyze the inhibitory effect of Nas on the proliferation、invasion ability and the induction of cell cycle arrest and apoptosis of MDA-MB-231 cells. Western blot analysis was performed to investigate the effects of Nas on the expression levels of cle-Caspase-3、PARP、cle-PARP、PLK1、PI3K、p-PI3K、AKT、p-AKT、CDK1、Cyclin B、Cyclin A、p-21、p-27、p-62、LC3、γ-H2AX proteins in MDA-MB-231 cells. Results Different concentrations of Nas (0.5 μmol/L, 1.0 μmol/L, 2.0 μmol/L) could inhibit the clone formation of MDA-MB-231 cell line (the 48 h inhibition rate was 15.99%, 24.76% and 54.17%, respectively), and the invasive ability (the 48 h inhibition rate was 0.68%, 23.20% and 45.27%, respectively). The cell cycle was blocked in G2 phase (the 48 h block rate was 75.50%, 140.56% and 316.06%, respectively) and apoptosis was induced (the 48 h apoptosis induction rates were 105.39%, 199.73% and 375.74%, respectively, and the 72 h apoptosis induction rates were 104.45%, 244.96% and 709.60%, respectively). Molecular mechanism experiments showed that Nas could significantly promote the expression of cle-Caspase-3, cle-PARP, γ-H2AX, p-21 and p-27, and significantly inhibit the expression of PLK1, p-PI3K, p-AKT, CDK1 and Cyclin B, but had no significant effect on the expression of PARP, p-62, LC3-II/I, PI3K and Cyclin A.Conclusion Nas can inhibit the clone formation and invasion of MDA-MB-231 cell line, induce apoptosis and block the cell cycle in G2 phase. This mechanism may be achieved by regulating the PLK1/AKT signal pathway. |
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