Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice.
Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice.
复制标题
抑制热休克蛋白90使肝癌干细胞样细胞对磁热疗法敏感并增强对肝癌裸鼠的抗肿瘤作用
DOI：
10.2147/ijn.s93758
复制
发表时间：
2015
影响因子：
8
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Yang R;Tang Q;Miao F;An Y;Li M;Han Y;Wang X;Wang J;Liu P;Chen R
目的探讨磁高温处理的人肝癌干细胞样细胞（LCSC）的耐热性、热休克蛋白90（HSP 90）表达以及热休克蛋白90抑制剂17-烯丙氨基-17-去甲氧格尔德霉素（17-AAG）对荷肝癌裸小鼠的影响。方法采用磁激活细胞分选法分离BEL-7404细胞中CD 90 + LCSC。进行球体形成、增殖、分化、耐药性和肿瘤形成测定以鉴定干细胞特征。采用反相蒸发法制备了以CD 90为靶点的17-AAG磁性热敏脂质体（CD90@17-AAG/TMs），并对其性质进行了研究。在体外和体内检测CD 90 + LCSC的耐热性和CD90@17-AAG/TMs介导的热敏感性的作用。结果CD 90 + LCSCs具有明显的干细胞样特性。成功制备了17-AAG/TM，其形状为球形，平均尺寸为128.9± 7.7nm。当暴露于磁热疗时，HSP 90在CD 90 + LCSC中上调。CD90@17-AAG/TMs可抑制HSP 90活性，增加CD 90 + LCSC对磁热疗的敏感性。结论抑制HSP 90可使CD 90 + LCSCs对磁热疗敏感，增强其体内外抗肿瘤效应。
Purpose To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice. Methods CD90+ LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90+ LCSCs and the effect of CD90@17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo. Results CD90+ LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9±7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90+ LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90+ LCSCs to magnetic hyperthermia. Conclusion The inhibition of HSP90 could sensitize CD90+ LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo.