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Chemosensitization of breast carcinoma cells with the use of bcl-2 antisense oligodeoxynucleotide

J H Yang1, F Feng, H Qian

  • 1Department of General Surgery, Shidong Hospital, Teaching Hospital of Shanghai, Second Medical University, Shidong Hospital, Shanghai 200090, China. yangjianhuicn@hotmail.com

Breast (Edinburgh, Scotland)
|June 5, 2004
PubMed

Insights

Combining bcl-2 antisense oligonucleotide (ASODN) with 5-fluorouracil (5-FU) significantly enhances breast cancer cell apoptosis. This synergistic effect increases cell death rates compared to using 5-FU alone.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • 5-fluorouracil (5-FU) is a common chemotherapy agent for breast cancer.
  • The bcl-2 gene plays a crucial role in regulating apoptosis (programmed cell death).
  • Inhibiting bcl-2 expression may sensitize cancer cells to chemotherapy.

Purpose of the Study:

  • To investigate if bcl-2 antisense oligonucleotide (ASODN) can enhance 5-FU-induced apoptosis in MCF-7 breast cancer cells.
  • To evaluate the combined cytotoxic effect of bcl-2 ASODN and 5-FU.

Main Methods:

  • MCF-7 cells were transfected with bcl-2 ASODN or control oligonucleotides.
  • bcl-2 gene expression was analyzed using Western blot.
  • Cell viability was assessed by MTT assay.
  • Apoptosis rates were quantified by flow cytometry (FCM).

Main Results:

  • Transfection with bcl-2 ASODN significantly reduced bcl-2 protein expression compared to controls.
  • Pre-treatment with bcl-2 ASODN followed by 5-FU resulted in a significant decrease in viable cells (P < 0.01).
  • FCM analysis showed a marked increase in apoptosis rates (29.8%) in the bcl-2 ASODN + 5-FU group compared to controls (8.0-16.5%).

Conclusions:

  • bcl-2 ASODN effectively downregulates bcl-2 expression in MCF-7 cells.
  • Combining bcl-2 ASODN with 5-FU demonstrates a synergistic cytotoxic effect, significantly enhancing apoptosis.
  • This combination therapy holds potential for improved breast cancer treatment strategies.

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