Year: 2012
Type: conference-paper
Abstract: One in four cases of breast cancer shows over expression of the Her-2 protein, and there is an urgent need to improve therapies for this disease. We have evaluated two Her-2 positive human breast cancer cell lines, MDA-231H2N and HCC1419. MDA-231 human breast cancer cell, which are Her-2 negative, were used as a control. The cell lines were evaluated in vitro for their relative growth rate, their growth under reduced (i.e. 3% serum) conditions, or as spheroid cultures, and for their sensitivity to drugs such as ceramide analogs and tyrosine kinase inhibitors (i.e. CLM3, CLM29, and CLM94) that are being evaluated in our laboratory.\nHer-2 transduced variants (MDA-231-H2N) showed a 50% increase in doubling rate and enhanced growth in low-serum media compared to MDA-231 cells. Only HCC1419 grew as compact spheroids, even 96 hours after plating on solidified agar.\nAll three cancer cell lines showed sensitivity to ceramide analogs and tyrosine kinase inhibitors tested. Following 48 hour treatment, the greatest cytotoxicity was observed with 25mM ceramide analog C6 (N-Hexanoyl-D-erythro-sphingosine), and 25mM of the tyrosine kinase inhibitor CLM29 (pyrazolo[3,4-d]pyrimidine). The activity of these agents was unaffected by Her-2 transduction or over expression. Our results provide additional characterization of available models of human Her-2 positive breast cancer cell lines, and suggest that the agents C6 and CLM29 merit further evaluation as potential anti-breast cancer agents.
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Science Foundation
OpenAlex ID: W580114093