| Autor: |
Soltani A; Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran., Torki S; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, PO Box 88155-571, Shahrekord, Iran., Ghahfarokhi MS; Department of Microbiology and Immunology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran., Jami MS; Department of Neurology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA., Ghatrehsamani M; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, PO Box 88155-571, Shahrekord, Iran. ghatreh.m@SKUMS.ac.ir. |
| Abstrakt: |
The phosphoinositide 3-kinase/AKT/mTOR (PI3K/AkT/mTOR) pathway plays a pivotal role in the uncontrolled growth, migration and development of human breast cancer. The elevated expression of TGF-β1 increases the PI3K/AkT/mTOR activity in human breast cancer tissue and potentially motivates tumor metastasis and resistance to chemotherapy. Here, we investigated whether treatment with PI3K/AkT/mTOR dual inhibitor NVP-BEZ235 alone or in combination with caffeic acid phenyl ester (CAPE) could prevent TGF-β1 effects on breast cancer cells. MCF-7 human breast cancer cells were exposed to TGF-β1 for 14 days and then were treated with/without NVP-BEZ235 and/or CAPE. Cell viability, apoptosis, CXCR4 surface expression and mRNA levels of CXCR4 and TWIST-1 were analyzed in all treated groups. We found that treatment of human breast cancer cells with a combination of NVP-BEZ235 and CAPE increased induction of cellular death. Although flow cytometry analysis demonstrated that NVP-BEZ235 alone treatment reduced CXCR4 expression while increasing CXCR4 mRNA level; when NVP-BEZ235 was combined with CAPE, inhibition of CXCR4 surface expression and enhancement of CXCR4 mRNA expression was diminished. In addition, TWIST-1 mRNA expression was down regulated in samples treated with both NVP-BEZ235 and CAPE. These altogether signified that NVP-BEZ235 in combination with CAPE showed improved therapeutic efficacy in breast cancer cells by decreasing apoptotic resistance and reduction of CXCR4 and TWIST-1 expression at mRNA level could be one of mechanism of action. |
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