Effect of eribulin on cell growth and PI3K pathway activity with and without RAD001 in triple-negative and HER2-expressing breast cancer

Autor:	Quanhua Xing, Ernest S. Han, M.L. Richard Yip, David Luyimbazi, Jin Yan, John H. Yim, Thehang Luu, Dylan Tully
Rok vydání:	2013
Předmět:	Cancer Research Cell growth business.industry P70-S6 Kinase 1 Pharmacology medicine.disease chemistry.chemical_compound Breast cancer Oncology chemistry SKBR3 medicine Growth inhibition business Protein kinase B PI3K/AKT/mTOR pathway Eribulin
Zdroj:	Journal of Clinical Oncology. 31:173-173
ISSN:	1527-7755 0732-183X
DOI:	10.1200/jco.2013.31.26_suppl.173
Popis:	173 Background: Patients with triple-negative breast cancer have high levels of Akt expression and activation of the PI3K-mTOR pathway. Eribulin is a microtubule-targeting agent with benefits in treating refractory triple negative disease. Our objective was to evaluate its efficacy in inhibiting PI3K pathway activity and cell growth both alone and in combination with the mTOR inhibitor RAD001. Methods: MDA468, BT549 and SKBR3 breast cancer cell lines were used for this study. MTT assays were used to assess growth inhibition after 72 hour treatment with eribulin alone and in combination with RAD001. Combination indices (CI) generated by Chou-Talalay plots were used to quantify synergy. Western blots were used to evaluate the expression of phosphorylated Akt-Ser473 (pAkt) and S6K1 after 24 hours of treatment with both agents. Results: Both MDA468 and SKBR3 cells treated with eribulin in varying concentrations showed inhibition of pAkt expression. Standard dilutions of eribulin in combination with log dilutions of RAD001 resulted in marked synergistic growth inhibition (CI<
Databáze:	OpenAIRE
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