Zhu Yanjing, Wu Youjun, Zhang Haixia, Wang Zhaoqi, Wang Shilong, Qian Yechang, Zhu Rongrong
J Biomed Nanotechnol. 2015 Dec;11(12):2158-68. doi: 10.1166/jbn.2015.2164.
Cell migration and invasion are integral to lung cancer metastasis. In this study, we investigated the combination of traditional chemotherapy and a layered double hydroxide (LDH) carrier as a new strategy for the inhibition of migration and invasion. To investigate the characteristics and possible mechanisms of VP16-LDH [the Mg-Al/LDH containing etoposide (VP16)], we used several experimental techniques, such as transmission electron microscopy (TEM) and fluorescent microscopy. The TEM, X-ray diffraction (XRD) and zeta potential results indicated that VP16 binds well with LDH, with an average size of 70 nm, and the drug delivery system was confirmed to have the desired quality of slow release by the in vitro release test results. Fluorescent images showed that the cellular uptake of VP16-LDH was a caveolae-mediated and energy-dependent process. Moreover, A549 cells treated with VP16-LDH (5 μg/ml, 10 μg/ml) demonstrated significant inhibition of cell migration and invasion compared with the cells treated with free VP16 at the same concentration. The inhibition of AKT, mTOR and STAT3 phosphorylation and p-β-catenin up-regulation in VP16-LDH-treated cells revealed a possible molecular mechanism via the mTOR/AKT and STAT pathways, through which VP16-LDH had a stronger inhibitory effect on migration than the drug alone.
细胞迁移和侵袭是肺癌转移的重要组成部分。在本研究中，我们研究了传统化疗与层状双氢氧化物（LDH）载体相结合作为抑制迁移和侵袭的新策略。为了研究VP16-LDH [含依托泊苷（VP16）的Mg-Al/LDH]的特性和可能机制，我们使用了几种实验技术，如透射电子显微镜（TEM）和荧光显微镜。TEM、X射线衍射（XRD）和zeta电位结果表明，VP16与LDH结合良好，平均粒径为70 nm，体外释放试验结果证实该药物递送系统具有所需的缓释质量。荧光图像显示，VP16-LDH的细胞摄取是一个小窝介导的、能量依赖的过程。此外，与相同浓度的游离VP16处理的细胞相比，用VP16-LDH（5μg/ml，10μg/ml）处理的A549细胞表现出对细胞迁移和侵袭的显著抑制。VP16-LDH处理的细胞中AKT、mTOR和STAT3磷酸化的抑制以及p-β-连环蛋白的上调揭示了一种可能通过mTOR/AKT和STAT途径的分子机制，通过该机制，VP16-LDH对迁移的抑制作用比单独使用药物更强。
