Effect of 1,25(OH)2D3 on the growth and apoptosis of breast cancer cell line MCF-7

Chin Med J (Engl). 2000 Feb;113(2):124-8.

Abstract

Objective: To study the effect of 1, 25-dihydroxyvitamin D3(1,25(OH)2D3) on the growth and apoptosis of breast cancer cell line MCF-7.

Methods: Cell number was determined using the MTT method. Flow cytometric analysis was performed on cell cycles, and the percentage of apoptosis was counted. Apoptotic cells were quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and bcl-2 protein expression was estimated with Western blotting.

Results: After incubation with 1,25(OH)2D3 10(-7) mol/L for 48 hours, MCF-7 cells exhibited significant growth in a dose- and time-dependent manner. Flow cytometric analysis indicated that cell numbers in G0/G1 increased along with increasing apoptotic peak and percentage. With microscope and electron microscope observation, characteristics of apoptosis such as typical apoptotic bodies were commonly found. TUNEL also showed that 1,25(OH)2D3 10(-8) mol/L and 10(-7) mol/L groups had significantly high apoptosis percentage than control group with dose-dependence on induction apoptosis. And Western blot showed that 1,25(OH)2D3 10(-8) mol/L could down-regulate bcl-2 protein and 10(-7) mol/L could almost block bcl-2 protein expression.

Conclusions: 1,25(OH)2D3 can inhibit cell growth with G0/G1 arrest, enhance the proliferation inhibition action of adriamycin, and induce apoptosis which may result from the down-regulation of the anti-apoptotic bcl-2 protein.

MeSH terms

  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / ultrastructure
  • Cell Cycle / drug effects
  • Cell Division / drug effects*
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Humans
  • In Situ Nick-End Labeling
  • Microscopy, Electron
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Steroid Hydroxylases / pharmacology*
  • Time Factors
  • Tumor Cells, Cultured / drug effects

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Steroid Hydroxylases
  • vitamin D 1-alpha hydroxylase