Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor

Lois M. Witters, Amy Stimpfel, Maricarmen D. Planas-Silva, Mark Berger, Jean Viallet, Allan Lipton

Research output: Contribution to journalArticle

Abstract

The epidermal growth factor receptor (EGFR) (ErbB1) and HER-2/neu (ErbB2) are members of the ErbB family of receptor tyrosine kinases. These receptors are overexpressed in a variety of human tumors and overexpression generally correlates with poor prognosis and decreased survival. Lapatinib, a reversible inhibitor of both EGFR and HER-2/neu, has shown some success in achieving clinical responses in heavily pretreated advanced cancer patients. GW2974 is a reversible dual inhibitor similar to lapatinib, but GW2974 was not progressed to clinical trials due to pharmacokinetic issues. Bcl-2, an anti-apoptotic protein, is also overexpressed in a number of human tumors. Bcl-2 inhibitors induce apoptosis and sensitize cancer cells to other therapies. The purpose of this study was to assess the effects of combining ErbB and Bcl-2 inhibitors on the growth of human breast cancer cell lines. EGFR/HER-2/neu tyrosine kinase inhibitors (lapatinib and GW2974) were combined with Bcl-2 inhibitors (HA14-1 or GX15-070) and the anti-proliferative effects were determined by the MTT tetrazolium dye assay. Combinations were tested in MCF-7 human breast cancer cells, a HER-2/neu transfected MCF-7 cell line (MCF/18), and a tamoxifen-resistant MCF-7 cell line (MTR-3). A synergistic inhibitory effect was observed with the combination of inhibitors of EGFR-HER-2/neu (lapatinib or GW2974) and Bcl-2 (GX15-070 or HA14-1) on the growth of the MCF-7, MCF/18, and MTR-3 human breast cancer cell lines. This study suggests that simultaneously blocking the ErbB family of receptor tyrosine kinases and Bcl-2 family of proteins may be a benefit to breast cancer patients.

Original languageEnglish (US)
Pages (from-to)465-469
Number of pages5
JournalOncology Reports
Volume17
Issue number2
StatePublished - Feb 2007

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Epidermal Growth Factor Receptor
Breast Neoplasms
Cell Line
TYK2 Kinase
MCF-7 Cells
Neoplasms
Growth Inhibitors
Apoptosis Regulatory Proteins
Tamoxifen
Protein-Tyrosine Kinases
Coloring Agents
Pharmacokinetics
Inhibition (Psychology)
Clinical Trials
Apoptosis
Survival
lapatinib
GW2974
Growth
Proteins

Keywords

  • Bcl-2
  • Breast cancer
  • ErbB
  • Growth inhibition
  • Synergism

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Witters, L. M., Stimpfel, A., Planas-Silva, M. D., Berger, M., Viallet, J., & Lipton, A. (2007). Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor. Oncology Reports, 17(2), 465-469.

Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor. / Witters, Lois M.; Stimpfel, Amy; Planas-Silva, Maricarmen D.; Berger, Mark; Viallet, Jean; Lipton, Allan.

In: Oncology Reports, Vol. 17, No. 2, 02.2007, p. 465-469.

Research output: Contribution to journalArticle

Witters, LM, Stimpfel, A, Planas-Silva, MD, Berger, M, Viallet, J & Lipton, A 2007, 'Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor', Oncology Reports, vol. 17, no. 2, pp. 465-469.
Witters, Lois M. ; Stimpfel, Amy ; Planas-Silva, Maricarmen D. ; Berger, Mark ; Viallet, Jean ; Lipton, Allan. / Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR-HER-2/neu and a Bcl-2 inhibitor. In: Oncology Reports. 2007 ; Vol. 17, No. 2. pp. 465-469.
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