阿霉素与纳米金刚石偶联和游离形式使胶质母细胞瘤细胞向异向命运分化。
Doxorubicin conjugated with nanodiamonds and in free form commit glioblastoma cells to heterodromous fates.
机构信息
Department of Pharmacology, School of Basic Medicine, Wuhan University, Donghu Avenue No. 185, Wuhan 430072, China.
Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
出版信息
Nanomedicine (Lond). 2019 Feb;14(3):335-351. doi: 10.2217/nnm-2018-0330. Epub 2019 Jan 24.
AIM
To mechanistically compare the effects of doxorubicin (DOX) and DOX conjugated with nanodiamonds (Nano-DOX) on human glioblastoma cells (GC).
MATERIALS & METHODS: GC viablity, proliferation and activation of apoptosis and autophagy was assayed in response to DOX and Nano-DOX. Expression and release of HMGB1 were measured and its role in apoptosis and autophagy probed in response to DOX and Nano-DOX. Results: DOX induced apoptosis in GC while Nano-DOX induced autophagy. Inhibition of autophagy in Nano-DOX-treated GC promoted apoptosis. DOX suppressed the emission of HMGB1 while Nano-DOX stimulated HMGB1 emission which was attenuated when autophagy was repressed. Blocking of HMGB1 emission mitigated autophagy and enhanced apoptosis in Nano-DOX-treated GC. Exogenously administered HMGB1 promoted autophagy and protected against apoptosis in both Nano-DOX-treated GC and DOX-treated GC.
CONCLUSIONS
Nano-DOX is a potent autophagy activator as opposed to DOX as an apoptosis inducer. Nano-DOX initiates a mutual reinforcement loop between autophagy and HMGB1 in GC and thereby protects GC against apoptosis.
目的
从机制上比较阿霉素（DOX）和与纳米金刚石（Nano-DOX）偶联的 DOX 对人神经胶质瘤细胞（GC）的影响。
材料与方法
检测 DOX 和 Nano-DOX 对 GC 活力、增殖、凋亡和自噬激活的影响。检测 DOX 和 Nano-DOX 作用下 HMGB1 的表达和释放，并探讨其在凋亡和自噬中的作用。
结果
DOX 诱导 GC 凋亡，而 Nano-DOX 诱导自噬。Nano-DOX 处理的 GC 中自噬抑制促进凋亡。DOX 抑制 HMGB1 的释放，而 Nano-DOX 刺激 HMGB1 的释放，自噬受到抑制时则减弱。阻断 HMGB1 的释放减轻了 Nano-DOX 处理的 GC 中的自噬并增强了凋亡。外源性给予 HMGB1 促进了自噬，并在 Nano-DOX 处理的 GC 和 DOX 处理的 GC 中均保护细胞免于凋亡。
结论
与诱导凋亡的 DOX 相反，Nano-DOX 是一种有效的自噬激活剂。Nano-DOX 在 GC 中引发自噬和 HMGB1 之间的相互增强循环，从而保护 GC 免于凋亡。
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