Cyclophosphamide exerts an anti-metastatic effect by reducing the expression of MMP-2 and -9 in Saos2 osteosarcoma cells

Abstract

Purpose: Although osteosarcoma is the most common primary malignant bone tumor among adolescents and young adults, the molecular mechanisms underlying the development of cancer are not fully elucidated. Cyclophosphamide (CYC) is an alkylating antineoplastic agent widely used in the treatment regimens of various cancers and chronic inflammatory diseases. The aim of this study is to reveal the effect of CYC on Saos-2 cells at the molecular level by determining the expression levels of some matrix metalloprotease proteins (MMP-2 and MMP-9) of cancer progression related genes. Materials and Methods: Cytotoxicity analyzes were performed by applying CYC to the developed human osteosarcoma (Saos-2) cell cultures. The determined dose of CYC was applied to the 2D cell lines for 12, 24 and 48 hours. As a result of agent application, the expression levels of MMPs, which are metastatic markers in these cultures, were determined by immunocytochemical method. Results: While MMP-2 and MMP-9 protein expression levels increased in the control (PBS) groups in correlation with the extend in duration in the cell cultures created; decreased with CYC administration. Conclusion: It was determined that the expression levels of genes that play a role in metastasis such as MMP-2 and MMP-9 were decreased by CYC application to Saos-2 cells. These results shed light on molecular studies for the treatment of osteosarcoma cancer.