Inhibitory effects of Chanling Gao on the proliferation and liver metastasis of transplanted colorectal cancer in nude mice

PLoS One. 2019 Feb 21;14(2):e0201504. doi: 10.1371/journal.pone.0201504. eCollection 2019.

Abstract

This study aimed to explore the efficacy and mechanism of Chanling Gao (CLG), a compound Chinese medicine, on colorectal cancer (CRC). A model of transplanted CRC was established in nude mice. The mice were treated 7 days after CRC transplantation with either Capecitabine or CLG for 3 weeks. On the 28th day after the operation, CRC growth and liver metastasis were assessed by morphology, the changes in the expression of HIF-1α (hypoxia inducible factor-1α), stromal cell-derived factor-1 alpha (SDF-1α), CXCR4 (C-X-C chemokine receptor type 4), PI3K, and Akt in the transplanted tumor and SDF-1α and CXCR4 in the liver were detected by Western blot and immunohistochemistry. The protein contents of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and collagen IV in the serum and transplanted tumor and SDF-1α and CXCR4 in liver tissues were detected by enzyme-linked immunosorbent assay. In the Capecitabine and high dose CLG groups, the growth and liver metastasis of CRC were significantly inhibited, the protein levels of HIF-1α, SDF-1α, CXCR4, MMP-2, VEGF, PI3K, Akt, P-PI3K and P-Akt in the transplanted tumor were lower, while the content of collagen IV in the transplanted tumor was higher, than in Model group. A high dose of CLG inhibited the growth of transplanted tumor and liver metastasis of CRC in nude mice, probably by inhibiting the HIF-1α/SDF-1α-CXCR4/PI3K-Akt signaling pathway reducing the synthesis and release of VEGF and degradation of collagen IV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Capecitabine / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemokine CXCL12 / metabolism
  • Colorectal Neoplasms / drug therapy*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunohistochemistry
  • Liver / metabolism
  • Liver Neoplasms / drug therapy
  • Male
  • Medicine, Chinese Traditional / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis / drug therapy
  • Phosphatidylinositol 3-Kinases / metabolism
  • Receptors, CXCR4 / metabolism
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Receptors, CXCR4
  • Vascular Endothelial Growth Factor A
  • Capecitabine
  • Phosphatidylinositol 3-Kinases

Grants and funding

This work was supported in part by National Natural Science Foundation of China (grant number: 81460697 and 81760814 to DXT and 81860819 to BY) and by Guizhou Province Traditional Chinese Medicine Modernization Project Foundation (SY-2014-3008-1 to DXT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.