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石蒜碱通过阻断Wnt/β-连环蛋白信号通路和上皮-间质转化(EMT),在非小细胞肺癌细胞中具有显著的抗癌潜力。

Lycorine possesses notable anticancer potentials in on-small cell lung carcinoma cells via blocking Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT).

作者信息

Sun Yanfang, Wu Pingping, Sun Yang, Sharopov Farukh S, Yang Qi, Chen Fangming, Wang Pan, Liang Zongsuo

机构信息

College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.

College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.

出版信息

Biochem Biophys Res Commun. 2018 Jan 1;495(1):911-921. doi: 10.1016/j.bbrc.2017.11.032. Epub 2017 Nov 7.

Abstract

Lycorine, an natural isoquinoline alkaloid has reportedly that possesses multi-anticancer activity. However, to date, the anticancer feature of lycorine in non-small cell lung carcinoma (NSCLC) has still not fully been spelled out. The present study mainly focused on the molecular mechanism of lycorine against NSCLC in vitro and vivo. The results showed that lycorine evidently inhibited proliferation of A549 and H460 with IC values were 10.83 ± 1.14 μM and 12.35 ± 1.13 μM, while caused slight cytotoxicity in normal pulmonary epithelial Beas-2B cells, and arrested cell cycle in G0/G1 phase. Hoechst DNA-binding staining showed that typical characteristics of nuclear morphology apoptosis, AnnexinV-FITC/PI staining revealed the early-period apoptosis and the dissipation of mitochondrial membrane potential (Δψm) were also captured after lycorine treatment. Moreover, lycorine effectively repressed the Wnt/β-catenin signaling and reversed epithelial-mesenchymal transition (EMT). In addition, lycorine also intervened the caspase-mediated mitochondrial apoptosis pathway. Furthermore, A549/Luc tumor xenograft model was also corroborated that lycorine significantly suppressed the growth and metastasis of the lung tumor. These data highlight the significance of lycorine as potential anti-neoplastic agents to combat NSCLC.

摘要

据报道,天然异喹啉生物碱石蒜碱具有多种抗癌活性。然而,迄今为止,石蒜碱在非小细胞肺癌(NSCLC)中的抗癌特性仍未完全阐明。本研究主要聚焦于石蒜碱在体外和体内抗NSCLC的分子机制。结果表明,石蒜碱明显抑制A549和H460细胞的增殖,IC值分别为10.83±1.14μM和12.35±1.13μM,而对正常肺上皮Beas-2B细胞仅产生轻微细胞毒性,并使细胞周期停滞于G0/G1期。Hoechst DNA结合染色显示出核形态凋亡的典型特征,AnnexinV-FITC/PI染色显示石蒜碱处理后出现早期凋亡,同时还检测到线粒体膜电位(Δψm)的消散。此外,石蒜碱有效抑制Wnt/β-连环蛋白信号通路并逆转上皮-间质转化(EMT)。另外,石蒜碱还干预了半胱天冬酶介导的线粒体凋亡途径。此外,A549/Luc肿瘤异种移植模型也证实石蒜碱显著抑制肺肿瘤的生长和转移。这些数据凸显了石蒜碱作为潜在抗肿瘤药物对抗NSCLC的重要意义。

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