Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells

Technol Cancer Res Treat. 2010 Feb;9(1):77-86. doi: 10.1177/153303461000900109.

Abstract

The successful of anti-cancer treatment are often limited by the development of drug resistance. Recent work has highlighted the involvement of non-coding RNAs, microRNAs(miRNAs) in cancer development, and their possible involvement in the evolution of drug resistance has been proposed. In this study, we combine taxol chemotherapy and miR-21 inhibitor treatment via polyamidoamine (PAMAM) dendrimers vector to evaluate the effects of combination therapy on suppression of breast cancer cells. The 50% inhibitory concentration (IC50) values for taxol were significantly decreased to a greater extent in the cells transfected with miR-21 inhibitor compared with cells treated with taxol alone. Taxol treatment also increased the percentage of apoptotic breast cancer cells in miR-21 inhibitor transfected cells compared with control cells. Furthermore, treatment of the miR-21 inhibitor-transfected cells with the anti-cancer drugs taxol resulted in significantly reduced cell viability and invasiveness compared with control cells. These results indicated that the miR-21 plays an important role in the resistance of breast carcinoma cells to chemotherapeutic drugs. Therefore, miR-21 inhibitor gene therapy combined with taxol chemotherapy might represent a promising novel therapeutic approach for the treatment of breast malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Cycle / drug effects
  • Cell Movement
  • Cell Proliferation / drug effects
  • Combined Modality Therapy
  • Dendrimers / pharmacology*
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy*
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Paclitaxel / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Transfection

Substances

  • Antineoplastic Agents, Phytogenic
  • Dendrimers
  • MIRN21 microRNA, human
  • MicroRNAs
  • PAMAM Starburst
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Paclitaxel