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Synergistic antitumor effect of NVP-BEZ235 and CAPE on MDA-MB-231 breast cancer cells

Triple negative breast cancer (TNBC) is the most lethal and aggressive kind of breast cancer. Studies with TNBC cells suggest that tumor environmental cytokines such as Transforming Growth Factor β1 (TGF-β1) have important roles in tumors fate. In the present study, we aimed to investigate, the effect of phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway dual inhibitor, NVP-BEZ235 and Caffeic acid phenyl ester (CAPE) on TNBC cell line (MDA-MB-231), stimulated with TGF-β1 for 14days in vitro. We found that TGF-β1 as a local tumor environmental cytokine plays important role in the progression and invasiveness of TNBC cells. NVP-BEZ235 inhibited the enhanced cell viability and CXCR4 expression induced by TGF-β1. In addition, the combined treatment of TNBC cell lines with CAPE and NVP-BEZ235 synergistically inhibited cell growth and reduced CXCR4 expression. Also, treatment of MDA-MB-231 cells with CAPE and NVP-BEZ235 led to decreasing the expression levels of p-FOXO3a in a time-dependent manner. Overall, these results suggest that tumor metastasis and progression in TNBC cells can be effectively reduced through the concurrent use of NVP-BEZ235 and CAPE. This could be of particular interest in assessing the effects of this therapy in the reduction of tumor metastasis and progression in other tumor types.

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Cat.No. Product Name Information
S1009 Dactolisib (BEZ235) Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2.

Related Targets

mTOR ATM/ATR PI3K