Determination of the Cytotoxic Effect of Deaminoneuraminic Acid Antibody in Breast Cancer Cells.
Project no. 20563 · Status: Kapanmış (Yayın bekleniyor) · 2019
Summary
Aim: Cancer is one of the diseases that result in death. For this reason, cancer treatment studies have increased considerably. Targeting cancer stem cells as well as destroying cancer cells is important in preventing the recurrence of cancer in the following years. Instead of classical cancer treatments such as chemotherapy and radiotherapy, treatment with target-specific monoclonal antibodies has gained importance. The basic mechanisms of action of monoclonal antibody treatments on cancer cells; complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), inhibition of signaling pathways that stimulate angiogenesis and cell proliferation. Deaminoneuraminic acid is a species of the sialic acid family. Deaminoneuraminic acid is more abundant in cancer and cancer stem cells than in normal cells. Therefore, deaminoneuraminic acid monoclonal antibody is a new and promising molecule in targeted therapies. In this study, the specific binding of deaminoneuraminic acid monoclonal antibody to breast cancer and cancer stem cells and its cytotoxic effect on cells were investigated. Method: MCF7 breast cancer cells and MCF10A breast epithelial cells were grown in culture. Cancer stem cells were collected from MCF7 cells by Fluorescent Activated Cell Sorting (FACS) method. The cytotoxicity of the antibody at different concentrations was examined with all the cell lines obtained and WST1 analysis was performed for this. Then, complement dependent cytotoxicity, antibody dependent cellular cytotoxicity and apoptosis experiments were performed to evaluate the effectiveness of the antibody. Conclusion: It has been observed that the monoclonal antibody does not work in the ADCC mechanism and creates an antagonistic effect between the CDC/ADCC mechanisms. Therefore, considering the CDC and apoptosis tests, it was determined that the 1/1000 concentration was the most effective dose. The damage of the antibody to the epithelial cells is negligible. In addition, it has been determined that it binds specifically to cancer and cancer stem cells and has apoptotic effect on these cells and cytotoxic effects with the complement system.