Tanshinone IIA reduces secretion of pro‑angiogenic factors and inhibits angiogenesis in human colorectal cancer

Oncol Rep. 2020 Apr;43(4):1159-1168. doi: 10.3892/or.2020.7498. Epub 2020 Feb 12.

Abstract

Tumor angiogenesis is an important factor which precipitates recurrence and metastasis of colorectal cancer (CRC). Angiogenesis is also a significant feature which accompanies invasion and metastasis of CRC. Tumor hypoxia activates hypoxia inducible factor (HIF), which promotes angiogenesis in CRC. HIF significantly promotes cell proliferation and angiogenesis in CRC, facilitating invasion and metastasis. Tanshinone IIA (Tan IIA) has been revealed to effectively inhibit angiogenesis in CRC, although the underlying mechanism remains to be determined. The aim of the present study was to determine the effects of HIF‑1α on hypoxia induced angiogenesis in CRC cells, the effects of Tan IIA on the expression of pro‑angiogenic factors in CRC cells, and on human umbilical vein endothelial cell (HUVEC) tube formation in normal and hypoxic conditions. The results of the present study revealed that Tan IIA not only decreased HIF‑1α expression and inhibited the secretion level of vascular endothelial growth factor and basic fibroblast growth factor, but also efficiently decreased proliferation, tube formation and metastasis of HUVECs. The results highlight the potential of Tan IIA‑mediated targeting of HIF‑1α as a potential therapeutic option for treatment of patients with CRC.

Keywords: tanshinone IIA; colorectal cancer; pro-angiogenic factors; hypoxic microenvironment; angiogenesis.

MeSH terms

  • Abietanes / pharmacology*
  • Angiogenesis Inducing Agents / metabolism*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / blood supply
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / prevention & control*
  • Signal Transduction
  • Tumor Hypoxia
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Abietanes
  • Angiogenesis Inducing Agents
  • Antineoplastic Agents, Phytogenic
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • tanshinone