Vimentin silencing effect on invasive and migration characteristics of doxorubicin resistant MCF-7 cells

Biomed Pharmacother. 2014 Apr;68(3):357-64. doi: 10.1016/j.biopha.2014.01.006. Epub 2014 Feb 13.

Abstract

Chemotherapy is one of the well-known treatments in cancer therapy. The effectiveness of chemotherapy is limited by several factors one of which is the emergence of multidrug resistance (MDR). One of the major mechanisms of MDR is the activity of several ATP binding cassette (ABC) transporters that pump drugs out of the cells. Doxorubicin intercalates and inhibits DNA replication; it is a powerful chemotherapeutic agent. However, it causes development of MDR in tumor cells. Vimentin is a type III intermediate filament protein that is expressed frequently in epithelial carcinomas correlating with invasiveness and also poor prognosis of cancer. There are several studies that have shown the connection between expression level of vimentin and invasiveness of tumor cells. In this study, MCF-7 cell line which is a model for human mammary carcinoma, and a doxorubicin resistant subline (MCF-7/Dox) were used. The resistant subline was previously obtained by stepwise selection in our laboratory. In the resistant cells, high levels of vimentin expression were observed. The main purpose of this study was to investigate changes in invasive and migration characteristics of MCF-7/Dox cell line, after transient silencing of vimentin gene by specific siRNA.

Keywords: Breast cancer; Cancer; Doxorubicin; Gene silencing; MCF-7; MDR; Metastasis; Vimentin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Blotting, Western
  • Cell Movement* / drug effects
  • Cell Movement* / genetics
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm* / drug effects
  • Drug Resistance, Neoplasm* / genetics
  • Flow Cytometry
  • Gene Silencing*
  • Humans
  • Immunohistochemistry
  • MCF-7 Cells
  • Neoplasm Invasiveness
  • RNA, Small Interfering / genetics
  • Transfection
  • Vimentin / genetics*

Substances

  • Antibiotics, Antineoplastic
  • RNA, Small Interfering
  • Vimentin
  • Doxorubicin