Investigation of drug resistance related to cell cycle control points in bortezomib resistant multiple myeloma cancer cell lines

Multiple Myeloma (MM) is a type of hematological cancer characterized by the accumulation of malignant plasma cells in the bone marrow. Bortezomib is one of the most effective chemotherapeutic drugs used clinically in the treatment of multiple myeloma. However, resistance to bortezomib is a frequently encountered situation during the cancer treatment process. In tumor cells, increased synthesis of drug transport proteins, suppression of apoptosis and changes in regulation factors involved in cell cycle control are the most important mechanisms that cause resistance to chemotherapeutic drugs. Therefore, in our study, the relationship between bortezomib resistance in multiple myeloma cancer cells and cyclin genes at cell cycle checkpoints was investigated. In this study, multiple myeloma KMS-28 (bortezomib-sensitive) and KMS-20 (bortezomib-resistant) cell lines were propagated. Bortezomib IC50 values were determined for both cell lines by applying the MTT test. cDNA synthesis was performed by RNA isolation from cell lines and the expression levels of the cell cycle regulatory factors Cyclin D1, Cyclin D2, Cyclin A1, Cyclin E1 and Cyclin B1 genes were analyzed by Real-Time PCR. According to our findings, the Cyclin A1 gene is not expressed at all in bortezomib-sensitive cells, and its high expression (overexpression) in bortezomib-resistant cells has shown that this gene has a direct role in the development of bortezomib resistance in multiple myeloma. The Cyclin D1 gene is overexpressed in KMS-28 and suppressed in KMS-20. It is thought that these changes in the Cyclin D1 gene may cause bortezomib resistance. In conclusion, elucidating the mechanisms leading to drug resistance in multiple myeloma will provide an understanding of the disease at the molecular level and will enable more effective treatment options for MM.