Yan Zhaokun, Wang Qingtang, Liu Xiaolong, Peng Jun, Li Qin, Wu Ming, Lin Jiumao
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine Fuzhou 350122 P. R. China
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. China
RSC Adv. 2018 Apr 27;8(29):15906-15914. doi: 10.1039/c8ra01071d.
Ursolic acid (UA) has shown great potential in cancer therapy but their efficacy is seriously compromised by poor water-solubility and limited cellular uptake. In this paper, cationic nanomicelles self-assembled from Pluronic F127 with the cationic polymer of C-polyethylenimine (C-PEI) as a functional component are fabricated as delivery vehicles of Chinese herbal medicine active components of ursolic acid (UA) for colorectal cancer treatment. The inhibition effects of this drug loaded cationic nanomicelles (named as FUP) on cell viability and cell colony formation were more significant than the free UA, due to their cationic surface which can increase UA uptake by colorectal cancer cells. Cell cycle analysis showed that this inhibition effect was mediated by a cell cycle arrest at the G1 checkpoint, and the cell death induced by these nanomicelles occurred apoptosis, which was detected by annexin V antibody and propidium iodide staining. Further western blot analysis demonstrated the apoptosis mechanism was associated with the regulation of Fas/FasL and activation of caspase-8 and caspase-3. Therefore, our cationic nanomicelles can potentially be used to enhance the therapeutic effect of UA for colorectal cancer treatment.
熊果酸（UA）在癌症治疗中显示出巨大潜力，但其疗效因水溶性差和细胞摄取受限而严重受损。在本文中，以Pluronic F127与阳离子聚合物C-聚乙烯亚胺（C-PEI）自组装形成的阳离子纳米胶束作为熊果酸（UA）这一中药活性成分的递送载体，用于治疗结直肠癌。这种载药阳离子纳米胶束（命名为FUP）对细胞活力和细胞集落形成的抑制作用比游离UA更显著，这是因为其阳离子表面可增加结直肠癌细胞对UA的摄取。细胞周期分析表明，这种抑制作用是由细胞在G1期检查点的阻滞介导的，这些纳米胶束诱导的细胞死亡为凋亡，通过膜联蛋白V抗体和碘化丙啶染色检测到。进一步的蛋白质印迹分析表明，凋亡机制与Fas/FasL的调节以及caspase-8和caspase-3的激活有关。因此，我们的阳离子纳米胶束有潜力用于增强UA对结直肠癌治疗的效果。
