Clinical Laboratory Medicine, First Affiliated Hospital, Anhui University of Science & Technology, Huainan, 232001, China.
J Biomed Nanotechnol. 2021 Nov 1;17(11):2247-2258. doi: 10.1166/jbn.2021.3194.
Radioresistance limits the effectiveness of radiotherapy for hepatocellular carcinoma. Raf and PI3K signaling cascades promote the formation of radioresistance in hepatocellular carcinoma (HCC). Lupeol has anticancer activity despite itspoor solubility in water and is toxic effect on normal tissue. In this study, nanoparticles (lupeol-NPs) were constructed using PEG-PLGA diblock copolymer vector, and results revealed that Lupeol-NPs reversed the radioresistance of hepatocellular carcinoma by inhibiting cellular proliferation and cell-cycle progression and promoting cellular apoptosis through blocking Raf/MAPK and PI3K/Akt signal transduction in radioresistant Huh-7 cells. , Lupeol-NPs combined with radiotherapy inhibited the growth of radioresistant hepatocellular carcinoma in a xenogenic nude mouse model. Ki-67 proliferation index decreased significantly ( < 0.05). We conclude that Lupeol-NPs can increase the sensitivity of radioresistant hepatocellular carcinoma to radiotherapy through inhibiting the Raf and PI3K signal cascades.
放射抗拒限制了肝癌的放射治疗效果。Raf 和 PI3K 信号级联促进肝癌（HCC）形成放射抗拒。尽管羽扇醇在水中的溶解度差且对正常组织有毒性作用，但它仍具有抗癌活性。在这项研究中，使用 PEG-PLGA 两亲嵌段共聚物载体构建了纳米颗粒（羽扇醇-NPs），结果表明，羽扇醇-NPs 通过阻断 Raf/MAPK 和 PI3K/Akt 信号转导，在耐辐射 Huh-7 细胞中抑制细胞增殖和细胞周期进程，促进细胞凋亡，从而逆转肝癌的放射抗拒。羽扇醇-NPs 联合放射治疗抑制了异种裸鼠模型中耐辐射肝癌的生长。Ki-67 增殖指数显著降低（<0.05）。我们得出结论，羽扇醇-NPs 通过抑制 Raf 和 PI3K 信号级联，可增加耐辐射肝癌对放射治疗的敏感性。
