Abstract Detail

Abstract

Background: Breast cancer (BC) cells often develop multiple mechanisms of chemo- and radio-resistance during tumor progression, which is the major reason for the failure of breast cancer therapy. Targeted nanomedicines have tremendous therapeutic potential in BC treatment over their free drug counterparts. Searching for chemo- and radio-sensitizers to overcome such resistance is therefore urgently required. The goal of this study is to evaluate and compare the chemo- and radio-sensitizers efficacy of amygdalin-folic acid-nanoparticles (AFA) on MCF-7 and MDA-MB-231 cells. 

Material and methods: The effects of AFA on MCF-7 and MDA-MB-231 cells proliferation and IC50, were assessed using MTT. The expression of proteins involved in several mechanisms induced by AFA in MCF-7 and MDA-MB-231 cells, including growth inhibition, apoptosis, tumor growth regulators, immune-modulators, and chemo‑radio-sensitizing activities of AFA on MCF-7 and MDA-MB-231 cells were evaluated via and flow cytometry and Elisa. 

Results: The results indicated that AFA inhibited proliferation, promoted apoptosis, cell cycle arrest at (G1 and sub G1) and suppressed tumor promotion in MCF-7 and MDA-MB-231 cells in a dose‑dependent manner. AFA treatment also induced the mitogen-activated protein kinases-downregulation protein kinase (MAPK/P38) with a concomitant reduction in the expression of tumor promoters signaling, including CD4, CD80, TGF-β, and Fe. In addition, AFA enhanced the chemosensitivity of MCF-7 and MDA-MB-231 cells to doxorubicin, a commonly used chemotherapy in breast cancer treatment. A combination of AFA and radiation enhanced apoptosis and increased the expression of two radiation‑induced DNA damage markers, CD8 and ROS. 

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