GDF3 inhibits the growth of breast cancer cells and promotes the apoptosis induced by Taxol

J Cancer Res Clin Oncol. 2012 Jun;138(6):1073-9. doi: 10.1007/s00432-012-1213-3. Epub 2012 Apr 10.

Abstract

Purpose: The aim of this study is to investigate whether GDF3 is related to the progression of human breast cancer and the effects of GDF3 on breast cancer cells.

Methods: The expression of GDF3 in 24 breast cancer specimens paired with corresponding neighboring nontumorous tissue was studied by Western blot. Breast cancer cells were treated with different concentrations of recombinant human GDF3 protein. Using lentivirus containing sh-RNA, we knocked down the expression of GDF3. Soft agar assay was performed to explore the effects of GDF3 on colony formation. Different anti-tumor drugs dealt with MCF-7 cells stably expressing GDF3.

Results: We found that GDF3 expression level was significantly down-regulated in breast cancer tissues compared to the surrounding nontumorous tissues. GDF3 proteins could inhibit the proliferation of MCF-7 and T47D cells. We also found that the knockdown of GDF3 resulted in the promotion of colony formation and enhanced the ability of anchorage-independent cell growth in soft agar. Furthermore, overexpression of GDF3 could promote the apoptosis induced by Taxol.

Conclusions: Our data indicated that GDF3 expression is significantly decreased in human breast cancer tissues, and reconstitution of GDF3 in breast cancer may be a potential therapeutic approach to inhibit aggressive growth of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Progression
  • Down-Regulation / drug effects
  • Female
  • Gene Knockdown Techniques / methods
  • Growth Differentiation Factor 3 / biosynthesis*
  • Growth Differentiation Factor 3 / genetics
  • Growth Differentiation Factor 3 / metabolism
  • Humans
  • Paclitaxel / pharmacology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tumor Stem Cell Assay / methods

Substances

  • Antineoplastic Agents
  • GDF3 protein, human
  • Growth Differentiation Factor 3
  • Recombinant Fusion Proteins
  • Paclitaxel