Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Aug;31(2):277-83.

Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells

Affiliations
  • PMID: 17611683

Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells

Hiroaki Kajiyama et al. Int J Oncol. 2007 Aug.

Abstract

The aim of this study was to assess paclitaxel resistant-epithelial ovarian carcinoma (EOC) cells for cellular morphology, motility, and molecular changes consistent with epithelial-mesenchymal transition (EMT). The human EOC cell lines NOS-2, TAOV and SKOV-3 were continuously exposed to increasing doses of paclitaxel to establish three stable cell lines resistant to paclitaxel (NOS-PR, TAOV-PR, and SKOV-PR cells, respectively). Using these cell lines, cellular functions such as motility, invasive ability, and proliferative potential were assessed. Several molecules involved in EMT or cell invasiveness were assessed using Western blot analysis. In a peritoneal metastasis model using mice inoculated with NOS-2 or NOS-PR cells, we investigated the differences of peritoneal dissemination and survival time. NOS2-PR cells showed phenotypic changes consistent with EMT; with spindle-shaped morphology and enhanced pseudopodia formation. Western blot analysis revealed decreased expression of the epithelial adhesion molecule, E-cadherin and an increase in mesenchymal markers such as vimentin, fibronectin and smooth-muscle actin in NOS-PR cells compared to NOS-2 cells. The NOS2-PR cells displayed increased expression of Snail and Twist, EMT-regulatory transcription factors. Migratory potential in a wound assay and metastatic potential to the peritoneum of mice were markedly enhanced in NOS2-PR cells compared to NOS-2 cells. These data suggest that there is a possible link between chronic paclitaxel-resistance and induction of the EMT in EOC cells. It is possible that therapeutic benefits such as the restoration of chemosensitivity or suppression of metastasis will be enabled by gaining further insight into the mechanisms underlying chemoresistance and EMT.

PubMed Disclaimer

Substances