1. Academic Validation
  2. Targeting UBR5 in hepatocellular carcinoma cells and precise treatment via echinacoside nanodelivery

Targeting UBR5 in hepatocellular carcinoma cells and precise treatment via echinacoside nanodelivery

  • Cell Mol Biol Lett. 2022 Oct 12;27(1):92. doi: 10.1186/s11658-022-00394-w.
Menghan Wang # 1 Xing Ma # 1 Guoyu Wang 1 Yanan Song 2 Miao Zhang 2 Zhongchao Mai 1 Borong Zhou 1 Ying Ye 3 Wei Xia 4
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, 358 Datong Rd, Pudong New Area, Shanghai, 200137, China.
  • 2 Central Laboratory, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, 358 Datong Rd, Pudong New Area, Shanghai, 200137, China.
  • 3 Central Laboratory, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, 358 Datong Rd, Pudong New Area, Shanghai, 200137, China. [email protected].
  • 4 Department of Nuclear Medicine, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, 358 Datong Rd, Pudong New Area, Shanghai, 200137, China. [email protected].
  • # Contributed equally.
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.

Keywords

Drug delivery; Echinacoside; Hepatocellular carcinoma; Nanoparticle; UBR5.

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