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Tumor Biology

, Volume 35, Issue 9, pp 9139–9146 | Cite as

Anti-tumor activity of oridonin on SNU-5 subcutaneous xenograft model via regulation of c-Met pathway

  • Hua Liu
  • Changlin Qian
  • Zhiyong Shen
Research Article

Abstract

Gastric cancer is the leading cause of cancer death worldwide. Oridonin, a diterpenoid isolated from Rabdosia rubescens, has attracted considerable attention as a potential treatment for gastric cancer based on its anti-tumor effects in many tumor cell lines. However, detailed anti-tumor mechanisms of oridonin remain a matter of speculation. In the present study, a gastric carcinoma cell line harboring c-Met gene amplification SNU-5 was used to investigate the underlying mechanisms. The results showed that in vitro, oridonin potently inhibited c-Met phosphorylation and c-Met-dependent cell proliferation (IC50 value, 36.8 μM), meanwhile down-regulated the expression of the downstream signaling molecules including phospho-c-Raf, phospho-Erk, and phospho-Akt. In vivo, oridonin showed efficacy at well-tolerated doses, including marked cytoreductive anti-tumor activity in SNU-5 subcutaneous xenograft model. The anti-tumor efficacy of oridonin was dose-dependent and showed strong inhibition of c-Met phosphorylation. Additional mechanism of action studies showed dose-dependent inhibition of c-Met-dependent signal transduction, tumor cell proliferation (Ki67), and reduction of microvessel density (CD31). These results suggested that the anti-tumor activity of oridonin may be mediated by direct effects on tumor cell growth or survival as well as anti-angiogenic mechanisms. In summary, the results indicated that oridonin exerted anti-tumor growth on human gastric cancer SNU-5 in vitro and in vivo by direct regulation of c-Met signaling pathway and the anti-tumor effects was mainly based on its anti-proliferation and anti-angiogenesis.

Keywords

Oridonin c-Met SNU-5 cell line Gastric cancer 

Notes

Conflicts of interest

None

Supplementary material

13277_2014_2178_MOESM1_ESM.docx (15 kb)
Supplementary Table S1 (DOCX 14 kb)
13277_2014_2178_Fig9_ESM.jpg (34 kb)
Supplementary Fig. S1

(JPEG 33 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of General Surgery, Ren Ji HospitalSchool of Medicine, Shanghai Jiao Tong UniversityShanghaiP.R. China

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