Effects of alpha-difluoromethylornithine on markers of proliferation, invasion, and apoptosis in breast cancer

Anticancer Res. 2010 Jun;30(6):2263-9.

Abstract

Aim: To examine changes in biomarkers expressed in breast tumors in response to patient treatment with the polyamine synthesis inhibitor alpha-difluoromethylornithine (DFMO).

Patients and methods: The expression of Ki-67 (MIB-1), matrix metalloproteinases (MMP) 2 and 9, urokinase-type plasminogen activator (uPA) were examined by immunohistochemistry in breast tissue specimens (controls: n=15, 13 evaluable, and DFMO group; n=27, 21 evaluable). Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL).

Results: Significant increases in apoptosis, MMP-9 and uPA (tumor) were observed in 7 patients >or=50 years who received DFMO for >or=14 days relative to patients <50 years and/or who received <14 days of treatment (n=11). No other measured characteristics, including tumor estrogen and progesterone receptor status, hormone replacement therapy history, histopathological characteristics or tumor grade were correlated with these biomarker changes.

Conclusion: Unexpected correlation of proapoptotic DFMO activity in postmenopausal women with breast cancer warrants further study.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Carcinoma, Intraductal, Noninfiltrating / drug therapy*
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Cell Proliferation / drug effects
  • Eflornithine / pharmacology*
  • Female
  • Humans
  • In Situ Nick-End Labeling
  • Ki-67 Antigen / analysis
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 9 / analysis
  • Middle Aged
  • Neoplasm Invasiveness

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Eflornithine