2. Academic Validation
  3. The role of daurisoline treatment in hepatocellular carcinoma: Inhibiting vasculogenic mimicry formation and enhancing sensitivity to sorafenib

The role of daurisoline treatment in hepatocellular carcinoma: Inhibiting vasculogenic mimicry formation and enhancing sensitivity to sorafenib

  • Phytomedicine. 2021 Nov:92:153740. doi: 10.1016/j.phymed.2021.153740.
Xue Zhang 1,  Ji-Gang Zhang 2,  Wan Mu 3,  He-Ming Zhou 2,  Gao-Lin Liu 4,  Qin Li 5
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China; Department of Pharmacy, Shanghai Eye Diseases Prevention & Treatment Center, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, 200040, China.
  • 2 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China.
  • 3 Department of Pharmacy, Shanghai Eye Diseases Prevention & Treatment Center, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, 200040, China.
  • 4 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China; Department of Pharmacy, Shanghai Eye Diseases Prevention & Treatment Center, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, 200040, China. Electronic address: [email protected].
  • 5 Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China. Electronic address: [email protected].
PMID: 34600176 DOI: 10.1016/j.phymed.2021.153740
Abstract

Background: Vasculogenic mimicry (VM) is a newly described tumor vascular phenomenon that is independent of traditional angiogenesis and provides an adequate blood supply for tumor growth. VM has been consistently observed in different Cancer types. Hence, inhibition of VM may be considered a new Anticancer therapeutic strategy.

Purpose: This study aimed to elucidate the potential Anticancer effect of daurisoline (DS) on hepatocellular carcinoma (HCC) and the potential molecular mechanism by which DS inhibits VM. We also verified whether combination treatment with sorafenib and DS constitutes a novel therapeutic approach to prevent HCC progression.

Methods: The effects of DS on proliferation were evaluated by Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. 4',6-Diamidino-2-phenylindole (DAPI) staining and flow cytometric analysis were employed to investigate its effects on Apoptosis. Western blot analysis, Matrigel tube formation assays, pulldown assays and immunofluorescence staining were applied to validate the potential mechanism by which DS inhibits VM. Mouse xenograft models were used to evaluate Anticancer activities.

Results: DS inhibited HCC cell proliferation, induced HCC cell Apoptosis and repressed VM formation by inactivating RhoA/ROCK2-mediated Akt and ERK-p38 MAPK signaling. Additionally, DS dramatically sensitized HCC cell lines to sorafenib, a curative Anticancer drug for patients with advanced HCC.

Conclusions: Our study provides insights into the molecular mechanisms underlying DS-induced inhibition of VM, which may facilitate the development of a novel clinical anti-HCC drug. Moreover, our findings suggest that the combination of DS and sorafenib constitutes a potential therapeutic strategy for HCC.

Keywords

Apoptosis; Daurisoline; Proliferation; Sorafenib; Vasculogenic mimicry.

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