Propofol inhibits invasion and enhances paclitaxel- induced apoptosis in ovarian cancer cells through the suppression of the transcription factor slug

Eur Rev Med Pharmacol Sci. 2013 Jul;17(13):1722-9.

Abstract

Background and aim: Propofol is one of the most commonly used intravenous anaesthetic agents during cancer resection surgery. It has recently found that propofol has the effect to inhibit cancer cell migration and invasion and sensitize cancer cells to chemotherapy. However, the role of the propofol on the ovarian cancer cells is unknown. In the present study, we explored the effect of propofol on invasion and chemosensitization of ovarian cancer cells to paclitaxel.

Materials and methods: The paclitaxel sensitivity of ovarian cancer cell lines HO-8910PM, H0-8910, SKOV-3, OVCAR-3, COC1 and ES-2 were determined by MTT assays. The Slug levels in the cell lines and the effects of propofol on Slug levels in the cell lines were determined by western blot assays. The effect of propofol on invasion, migration and paclitaxel-induced ovarian cancer apoptosis was determined by Boyden chamber assays, cell MTT, TUNEL assays.

Results: The results showed that the cell lines COC1, H0-8910 and ES-2 were sensitive, whereas HO-8910PM, OVCAR-3, SKOV-3, were resistant to paclitaxel. Significant correlation was observed between basal Slug levels and paclitaxel sensitivity. Paclitaxel treatment increased Slug levels. Treatment with propofol induced apoptosis and increased paclitaxel killing of all paclitaxel-sensitive and -resistant ovarian cancer cells followed by significant decrease in the Slug levels. Treatment with propofol inhibits invasion and migration.

Conclusions: These data suggest a new mechanism by which the propofol inhibits invasion and metastasis,enhances paclitaxel-induced ovarian cancer cell apoptosis through suppression of Slug.

MeSH terms

  • Anesthetics, Intravenous / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Female
  • Humans
  • In Situ Nick-End Labeling
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / pharmacology*
  • Propofol / pharmacology*
  • Snail Family Transcription Factors
  • Tetrazolium Salts
  • Thiazoles
  • Transcription Factors / drug effects*
  • Transcription Factors / genetics*

Substances

  • Anesthetics, Intravenous
  • Antineoplastic Agents, Phytogenic
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Tetrazolium Salts
  • Thiazoles
  • Transcription Factors
  • thiazolyl blue
  • Paclitaxel
  • Propofol