TTF1-NPs Induce ERS-Mediated Apoptosis and Inhibit Human Hepatoma Cell Growth In Vitro and In Vivo.
TTF1-NPs Induce ERS-Mediated Apoptosis and Inhibit Human Hepatoma Cell Growth In Vitro and In Vivo.
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TTF1-NP 在体外和体内诱导 ERS 介导的细胞凋亡并抑制人肝癌细胞生长
DOI：
10.3727/096504016x14567549091341
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发表时间：
2016
影响因子：
3.1
通讯作者：
Zhang XW
中科院分区：
文献类型：
--
作者：
Xiao B;Liu C;Liu BT;Zhang X;Liu RR;Zhang XW
已有研究表明，5，2 ′，4 ′-三羟基-6，7，5 ′-三甲氧基黄酮（TTF 1）是中药珍珠梅（Sorbaria sorbifolia，SS）的主要抗癌活性成分，在我国已被用于治疗癌症。本研究探讨了小分子TTF 1纳米粒（TTF 1-NPs）的体内外抗肿瘤作用及其生物学机制。使用人肝癌细胞研究TTF 1-NPs对细胞生长和凋亡的影响。通过免疫细胞化学和Western blot分析与TTF 1-NPs作用相关的分子变化。使用HepG 2肿瘤异种移植模型研究TTF 1-NP的体内作用。我们发现TTF 1-NPs在体外表现出抗肿瘤作用，并伴有诱导人肝癌细胞凋亡。从机制上讲，我们的数据表明TTF 1-NPs通过内质网应激（ERS）途径诱导肝癌细胞凋亡。此外，抑制ERS激活阻断TTF 1-NP诱导的HepG 2细胞凋亡。最后，TTF 1-NPs抑制HepG 2异种移植肿瘤的生长。综上所述，我们的研究结果表明TTF 1-NP诱导的细胞凋亡至少部分是由ERS通路介导的，从而抑制了肝癌肿瘤的生长。
Previous studies have shown that 5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone (TTF1) is the primary anticancer constituent of the traditional Chinese medicinal plant Sorbaria sorbifolia (SS), which has been applied to treat cancer in China. In this study, we investigated the in vitro and in vivo antitumor effects and biological mechanisms of small-molecule TTF1 nanoparticles (TTF1-NPs). The effects of TTF1-NPs on cell growth and apoptosis were investigated using human hepatoma cells. The molecular changes associated with the effects of TTF1-NPs were analyzed by immunocytochemistry and Western blot analysis. The in vivo effect of TTF1-NPs was investigated using the HepG2 tumor xenograft model. We found that TTF1-NPs exhibited antitumor effects in vitro accompanied by induction of apoptosis in human hepatoma cells. Mechanistically, our data showed that TTF1-NPs induced apoptosis via endoplasmic reticulum stress (ERS) pathway in hepatoma cells. Moreover, inhibition of ERS activation blocked TTF1-NP-induced apoptosis in HepG2 cells. Finally, TTF1-NPs inhibited the growth of HepG2 xenograft tumors. Taken together, our results demonstrated that TTF1-NP-induced apoptosis was mediated at least in part by the ERS pathway and thus inhibited hepatoma tumor growth.