[Primary study of vasculogenic mimicry induced by hypoxia in epithelial ovarian carcinoma]

Zhonghua Fu Chan Ke Za Zhi. 2005 Oct;40(10):662-5.
[Article in Chinese]

Abstract

Objective: To explore possibility of vasculogenic mimicry induced by hypoxia and the inhibitive effect by sirolimus in epithelial ovarian carcinoma in vitro.

Methods: Based on three-dimensional cell culture system developed by Matrigel, ovarian cell lines SKOV3 and ES2 were induced under conditions of hypoxia, hypoxia added with sirolimus and no-hypoxia, respectively. Potential formation of tumor channels and their characterization of network were observed by light microscopy and scanning electronic microscopy. Relative hypoxia-inducible factor (HIF) 1alpha mRNA expression was detected by RT-PCR simultaneously.

Results: The micrograph showed both SKOV3 and ES2 cells appeared expanded and re-shaped, then formed blood vessel-like structures such as cavity, channel, branch and network. These capabilities of cells were inhibited by sirolimus and no-hypoxia. The levels of HIF-1alpha mRNA expression of SKOV3 and ES2 were 0.801 +/- 0.034 and 0.736 +/- 0.059 under hypoxia, which were significantly higher than under hypoxia added with sirolimus (0.025 +/- 0.007, 0.231 +/- 0.035; P < 0.01, P < 0.05), and those under no-hypoxia (0.010 +/- 0.004, 0.011 +/- 0.002; both P < 0.01).

Conclusions: Hypoxia plays a key role in development of vasculogenic mimicry in epithelial ovarian carcinoma. Sirolimus can inhibit vasculogenic mimicry effectively by blocking HIF-1alpha at transcription level.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Cell Culture Techniques
  • Cell Hypoxia / physiology
  • Cell Line, Tumor
  • Collagen
  • Drug Combinations
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Laminin
  • Microscopy, Electron, Scanning
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / physiopathology
  • Neovascularization, Pathologic / prevention & control
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / ultrastructure
  • Proteoglycans
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sirolimus / pharmacology*

Substances

  • Antibiotics, Antineoplastic
  • Drug Combinations
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Laminin
  • Proteoglycans
  • RNA, Messenger
  • matrigel
  • Collagen
  • Sirolimus