Nasim Hassani - Department of biology, Faculty of Science, Tabriz branch Islamic Azad University, Tabriz, Iran
Mehdi Dadashpour - Department of Medical Biotechnology, Faculty of Advance Medical Science, Tabriz University of Medical Science, Tabriz, Iran
Leila Khoshravan - Department of, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Nosratollah Zarghami - Department of Clinical Biochemistry, faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran

Introduction: Breast cancer is the most common cancer in women. Molecular target therapy is a new treatment, refers to treatment with a new generation of cancer drugs designed to interfere with a specific molecular target, that have a critical role in tumor progression and proliferation. Cell cycle molecules have been considered as molecules target for breast cancer target therapy. Phytochemicals, can either modulate signaling pathway leading to cell cycle regulation or directly alter cell cycle regulatory molecules, can be used in cancer therapy. The low bioavailability and short half-life of this phytochemicals, hamper their application as an anticancer drug. Loading inside PLGA-PEG increase their solubility and drug tolerance and decreases the side effects of the drug. Resent studied suggest that combination of anti-tumor phytochemicals can be more effective in modulating different signaling pathways associated with tumor cell growth. The purpose of this study was to investigate the synergistic antiproliferative effect of combined Metformin and Artemisinin, two phytochemicals, on cell cycle arrest of breast cancer cells.Methods: The PLGA-PEG was prepared by ring-opening polymerization method. The structure of PLGA-PEG was evaluated by using FT-IR and SEM. The cytotoxic effect of individual and combined drugs on T47D cells were evaluated by MTT assay. The cell cycle distribution was analyzed by flowcytometry.Result: The MTT assay and flowcytometry results show that each compound exerted cytotoxic effects on T47D cells, both in time and dose-dependent manner. Met–Art–PLGA/PEG NPs had more synergistic antiproliferative effect and significantly arrested the growth of T47D cells than the other groups.Conclusions: The results provide evidence that synergistic anti proliferative effect of combined Metformin and Artemisinin lead to cell cycle arrest of breast cancer cells and suggest their combination in nanoparticles have therapeutic value in treatment of breast cancer.

Metformin, Artemisinin n, PLGA/PEG, synergistic effect, breast cancer