Hemn Mohammadpour1, Reza Fekrazad2. 1. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 2. Periodontology Department, AJA University of Medical Sciences, Tehran, Iran; Laser Research Center in Medical Sciences, AJA University of Medical Sciences, Tehran, Iran. Electronic address: rezafekrazad@gmail.com.
Abstract
BACKGROUND: Dickkopf 3 (Dkk-3), a Wnt signaling inhibitor, is a characterized DKK family member that efficiently suppresses tumor growth in several types of cancer. Photodynamic therapy (PDT) is commonly used for treatment of different types of cancer and antitumor efficacy of PDT increased upon Wnt signaling inhibition. The objective of this study is to evaluate the effects of Dkk-3 and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer cell line. MATERIAL AND METHODS: 4T1 breast cell line were treated with either Dkk-3 (20, 40 and 80ng/ml) 24h followed by 5-ALA-PDT (1, 3 and 6J/cm2). Also, 5-ALA was used at dose 1mM. The apoptosis and post apoptotic necrosis were evaluated by FITC-Annexin-PI apoptosis detection kit. RESULTS: Obtained findings showed that both Dkk-3 and ALA-PDT have cytotoxic effects on cancer cells in a dose-dependent manner. The subtracted mean of death cell percentage in 20, 40 and 80ng/ml of Dkk-3 were 6.8±0.7%, 10.4±0.84% and 16.1±1.55% respectively. The subtracted mean of cell death induction in 5-ALA mediated PDT was 5.3±0.77% at 6J/cm2. Dkk-3 with ALA-PDT significantly increased cell death compared to either Dkk-3 or 5-ALA mediated PDT in cancer 4T1 cancer cell line (P˂0.001). CONCLUSION: In this study, observed results revealed that Dkk-3 induced the apoptosis in 4T1 breast cancer cells and apoptotic effects of Dkk-3 intensified following photodynamic therapy. This study provided a novel insight into the development of therapeutic strategies for treatment of breast cancer using Dkk-3 combined with PDT.
BACKGROUND:Dickkopf 3 (Dkk-3), a Wnt signaling inhibitor, is a characterized DKK family member that efficiently suppresses tumor growth in several types of cancer. Photodynamic therapy (PDT) is commonly used for treatment of different types of cancer and antitumor efficacy of PDT increased upon Wnt signaling inhibition. The objective of this study is to evaluate the effects of Dkk-3 and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer cell line. MATERIAL AND METHODS: 4T1 breast cell line were treated with either Dkk-3 (20, 40 and 80ng/ml) 24h followed by 5-ALA-PDT (1, 3 and 6J/cm2). Also, 5-ALA was used at dose 1mM. The apoptosis and post apoptotic necrosis were evaluated by FITC-Annexin-PI apoptosis detection kit. RESULTS: Obtained findings showed that both Dkk-3 and ALA-PDT have cytotoxic effects on cancer cells in a dose-dependent manner. The subtracted mean of death cell percentage in 20, 40 and 80ng/ml of Dkk-3 were 6.8±0.7%, 10.4±0.84% and 16.1±1.55% respectively. The subtracted mean of cell death induction in 5-ALA mediated PDT was 5.3±0.77% at 6J/cm2. Dkk-3 with ALA-PDT significantly increased cell death compared to either Dkk-3 or 5-ALA mediated PDT in cancer 4T1 cancer cell line (P˂0.001). CONCLUSION: In this study, observed results revealed that Dkk-3 induced the apoptosis in 4T1 breast cancer cells and apoptotic effects of Dkk-3 intensified following photodynamic therapy. This study provided a novel insight into the development of therapeutic strategies for treatment of breast cancer using Dkk-3 combined with PDT.