Robotic Mammosphere Assay for High-Throughput Screening in Triple-Negative Breast Cancer
| Autor: | Göran Landberg, Paul A. Fitzpatrick, Elin M. V. Söderberg, Nina Akrap, G J Thomson, Hannah Harrison |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Oncology
Pathology medicine.medical_specialty medicine.medical_treatment High-throughput screening Antineoplastic Agents Apoptosis Triple Negative Breast Neoplasms Biochemistry Analytical Chemistry chemistry.chemical_compound Breast cancer Robotic Surgical Procedures Cancer stem cell Cell Line Tumor Internal medicine medicine Humans Salinomycin Triple-negative breast cancer Pyrans business.industry medicine.disease High-Throughput Screening Assays chemistry High-content screening Neoplastic Stem Cells Molecular Medicine Female Stem cell business Adjuvant Biotechnology |
| Zdroj: | SLAS Discovery. 22:827-836 |
| ISSN: | 2472-5552 |
| DOI: | 10.1177/2472555217692321 |
| Popis: | In order to identify novel treatment principles specifically affecting cancer stem cells in triple-negative breast cancer, we have developed a high-throughput screening method based on the mammosphere and anoikis resistance assays allowing us to screen compounds using a functional readout. The assay was validated against manual protocols and through the use of positive controls, such as the response to hypoxia and treatment with the known cancer stem cell-targeting compound salinomycin. Manual and robotic procedures were compared and produced similar results in cell handling, cell cultures, and counting techniques, with no statistically significant difference produced from either method. The variance between samples processed manually versus robotically was no greater than 0.012, while Levene's test of significance was 0.2, indicating no significant difference between mammosphere data produced manually or robotically. Through the screening of 989 FDA-approved drugs and a follow-up screen assessing the antineoplastic subgroup, we have identified three therapeutic compounds with the ability to modulate the breast cancer stem cell fraction in the triple-negative breast cancer cell line MDA-MB-231, highlighting their potential usage as stem cell-specific adjuvant treatments. |
| Databáze: | OpenAIRE |
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