2. Academic Validation
  3. Rheum palmatum extract exerts anti-hepatocellular carcinoma effects by inhibiting signal transducer and activator of transcription 3 signaling

Rheum palmatum extract exerts anti-hepatocellular carcinoma effects by inhibiting signal transducer and activator of transcription 3 signaling

  • J Ethnopharmacol. 2019 Mar 25;232:62-72. doi: 10.1016/j.jep.2018.12.019.
Zhang-Bin Tan 1,  Hui-Jie Fan 2,  Yu-Ting Wu 3,  Ling-Peng Xie 4,  Yi-Ming Bi 5,  Hong-Lin Xu 6,  Hong-Mei Chen 7,  Jun Li 8,  Bin Liu 9,  Ying-Chun Zhou 10
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 2 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 3 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 4 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 5 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 6 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 7 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 8 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 9 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Guangzhou Institute of Cardiovascular Disease, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. Electronic address: [email protected].
  • 10 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
PMID: 30553869 DOI: 10.1016/j.jep.2018.12.019
Abstract

Ethnopharmacological relevance: Hepatocellular carcinoma (HCC) is among the most common malignancies. Signal transducer and activator of transcription 3 (STAT3), with abnormal expression and constitutive activation, has been reported to promote proliferation, metastasis, survival and angiogenesis of HCC cells. Rheum palmatum (RP), a traditional Chinese medicinal herb, exhibited tumor-suppressing effects in multiple human cancers, but its potential functions in HCC remain unexplored.

Aim of the study: This study aimed to examine the involvement of STAT3 signaling in the anti-HCC effects of RP extract.

Materials and methods: SMMC-7721 and HepG2 HCC cell lines were treated with RP extract for 24 h, and then viability, migration, and invasion of HCC cells and angiogenesis of human umbilical vein endothelial cells (HUVECs) were analyzed using MTS, wound-healing, Transwell invasion and tube formation assays, respectively. Western blotting and immunohistochemistry (IHC) were used to examine the activation of key molecules in STAT3 signaling, including STAT3, JAK2, and Src. Additionally, we explored the in vivo antitumor effects of RP extract in a xenograft tumor nude mouse model of HCC.

Results: The result showed that RP extract reduced viability, migration, and invasion of SMMC-7721 and HepG2 cells and angiogenesis of HUVECs. It suppressed the phosphorylation of STAT3 and its upstream kinases including JAK2 and Src. In addition, RP extract treatment downregulated STAT3 target genes, including Survivin, Bcl-xL, Mcl-1, Bcl-2, MMP-2, MMP-9, Cyclin D1, CDK4, c-Myc, and VEGF-C. Furthermore, RP extract suppressed the xenograft tumor growth and activation of STAT3 in xenograft tumor mice.

Conclusion: Collectively, the results showed that RP extract prevented HCC progression by inhibiting STAT3, and might be useful for the treatment of HCC.

Keywords

Hepatocellular carcinoma; Rheum palmatum; STAT3.

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