Targeting UBR5 in hepatocellular carcinoma cells and precise treatment via echinacoside nanodelivery.
Targeting UBR5 in hepatocellular carcinoma cells and precise treatment via echinacoside nanodelivery.
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靶向肝癌细胞UBR5及松果菊苷精准治疗
DOI：
10.1186/s11658-022-00394-w
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发表时间：
2022-10-12
影响因子：
8.3
通讯作者：
中科院分区：
文献类型：
--
作者：
肝细胞癌（Hepatocellular carcinoma，HCC）是最常见的恶性肿瘤之一，目前尚无有效的治疗方法.松果菊苷（Echinacoside，ECH）是从中草药盐生肉苁蓉（Cistanchessalsa）中分离得到的一种苯乙醇苷类化合物，具有抑制肝癌进展的作用，但吸收差、生物利用度低限制了其生物学应用。为了提高ECH对HepG 2细胞的敏感性，我们开发了一种基于介孔二氧化硅纳米颗粒（MSN）的药物递送系统，通过半乳糖（GAL）和聚（乙二醇）二缩水甘油醚（PEGDE）缀合（ECH@Au@MSN-PEGDE-GAL，或ECH@AMPG）将ECH递送至HepG 2细胞。进行功能获得和丧失测定以评估UBR 5对HCC细胞凋亡和糖酵解的影响。此外，还研究了中间产物之间的相互作用，以阐明UBR 5的功能机制。本研究表明，泛素蛋白连接酶E3组分N-识别素5（UBR 5）作为癌基因在肝癌组织中，其表达被抑制ECH。AMPG显示出高载药量特性和随时间的缓慢和持续释放模式。此外，由于有效的药物蓄积作用，ECH@AMPG在体外可促进HepG 2细胞凋亡，抑制细胞糖酵解。体内实验表明，AMPG也增强了ECH在HepG 2细胞荷瘤小鼠中的抗肿瘤作用。我们的研究结果表明UBR 5作为治疗靶点的临床意义。基于AMPG的无毒和高载药能力，ECH@AMPG对肝癌细胞的作用优于游离ECH，显示了其在肝癌化疗中的潜力。在线版本包含补充材料，可通过10.1186/s11658-022-00394-w获得。
Hepatocellular carcinoma (HCC) is among the most common and malignant cancers with no effective therapeutic approaches. Echinacoside (ECH), a phenylethanoid glycoside isolated from Chinese herbal medicine, Cistanche salsa, can inhibit HCC progression; however, poor absorption and low bioavailability limit its biological applications. To improve ECH sensitivity to HepG2 cells, we developed a mesoporous silica nanoparticle (MSN)-based drug delivery system to deliver ECH to HepG2 cells via galactose (GAL) and poly(ethylene glycol) diglycidyl ether (PEGDE) conjugation (ECH@Au@MSN-PEGDE-GAL, or ECH@AMPG). Gain- and loss-of-function assays were conducted to assess the effects of UBR5 on HCC cell apoptosis and glycolysis. Moreover, the interactions among intermediate products were also investigated to elucidate the mechanisms by which UBR5 functions. The present study showed that ubiquitin protein ligase E3 component N-recognin 5 (UBR5) acted as an oncogene in HCC tissues and that its expression was inhibited by ECH. AMPG showed a high drug loading property and a slow and sustained release pattern over time. Moreover, owing to the valid drug accumulation, ECH@AMPG promoted apoptosis and inhibited glycolysis of HepG2 cells in vitro. In vivo experiments demonstrated that AMPG also enhanced the antitumor effects of ECH in HepG2 cell-bearing mice. Our results indicated the clinical significance of UBR5 as a therapeutic target. On the basis of the nontoxic and high drug-loading capabilities of AMPG, ECH@AMPG presented better effects on HCC cells compared with free ECH, indicating its potential for the chemotherapy of HCC. The online version contains supplementary material available at 10.1186/s11658-022-00394-w.
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影响因子：
5.2
作者：
Martinez-Iglesias, Olaia;Casas-Pais, Alba;Figueroa, Angelica
通讯作者：
Figueroa, Angelica
影响因子：
19
作者：
Manzano, Miguel;Vallet-Regi, Maria
通讯作者：
Vallet-Regi, Maria
影响因子：
4.2
作者：
Wang, Kai;Tang, Jun;Zheng, Rui
通讯作者：
Zheng, Rui
影响因子：
3.9
作者：
Bi, Haoran;Liu, Yupeng;Zhao, Yashuang
通讯作者：
Zhao, Yashuang
影响因子：
3.4
作者：
Li, Fei;Yang, Xiaolin;Zhang, Chunfeng
通讯作者：
Zhang, Chunfeng