Author:
Wang Menghan,Ma Xing,Wang Guoyu,Song Yanan,Zhang Miao,Mai Zhongchao,Zhou Borong,Ye Ying,Xia Wei
Abstract
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Funder
National Natural Science Foundation of China
Budgetary Fund of Shanghai University of TCM
leading talent Training Program of Pudong Health Burea of Shanghai
General project of Shanghai Municipal Health Commission
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
8 articles.
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