Shanghai Xuhui District Dental Disease Center, Shanghai, China.
Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Oral Dis. 2022 Jan;28(1):142-149. doi: 10.1111/odi.13751. Epub 2020 Dec 20.
Increasing evidence indicates that andrographolide (ADG) exhibits anti-cancer activity against various cancer cell lines. However, its high hydrophobicity and poor bioavailability restrict its clinical application as a chemopreventative agent. Previously, we have shown that ADG-loaded solid lipid nanoparticles (SLNs) significantly enhanced the bioavailability and anti-hyperlipidemic activity of ADG.
We aimed to investigate whether ADG-SLN enhanced the bioavailability and anti-cancer efficacy of ADG in the human immortalized oral epithelial (HIOEC), precancerous leukoplakia (Leuk1), HN6, and HN30 cells that represented an in vitro model of stepwise head and neck squamous cell carcinoma development.
The 50% inhibitive concentration (IC50) of ADG-SLN was significantly lower than that of free ADG against HIOEC, Leuk1, and HN6 and HN30 cells. Moreover, ADG-SLN was more effective than free ADG in promoting cell cycle arrest and apoptosis. Importantly, intracellular absorption of ADG was significantly higher in HN6 cells treated with ADG-SLN compared with free ADG-treated cells.
Our preliminary study demonstrates that ADG-SLN exhibits superior inhibitory activity against head and neck cancer and precancerous cells compared with free ADG. This effect is due to the higher efficiency of cellular uptake and intracellular absorption by ADG-SLN.
越来越多的证据表明，穿心莲内酯（ADG）对多种癌细胞系表现出抗癌活性。然而，其高疏水性和较差的生物利用度限制了其作为化学预防剂的临床应用。此前，我们已经表明，载穿心莲内酯固体脂质纳米粒（SLN）显著提高了 ADG 的生物利用度和抗高血脂活性。
我们旨在研究 ADG-SLN 是否增强了 ADG 在人永生化口腔上皮（HIOEC）、癌前白斑（Leuk1）、HN6 和 HN30 细胞中的生物利用度和抗癌疗效，这些细胞代表了头颈部鳞状细胞癌发展的体外模型。
ADG-SLN 对 HIOEC、Leuk1 和 HN6 和 HN30 细胞的 50%抑制浓度（IC50）明显低于游离 ADG。此外，ADG-SLN 在促进细胞周期停滞和凋亡方面比游离 ADG 更有效。重要的是，与游离 ADG 处理的细胞相比，HN6 细胞用 ADG-SLN 处理后 ADG 的细胞内吸收明显更高。
我们的初步研究表明，ADG-SLN 对头颈部癌症和癌前细胞的抑制活性明显优于游离 ADG。这种效果是由于 ADG-SLN 具有更高的细胞摄取和细胞内吸收效率。
