Abstract
Abstract Background Multiple myeloma (MM), a malignancy of plasma cells, is the second most prevalent hematological cancer. Bortezomib is the most effective chemotherapeutic drug used in treatment. However, drug-resistance prevents success of chemotherapy. One of the factors causing drug-resistance is dysfunction of apoptotic-pathways. This study aimed to evaluate the relationship between expression levels of Bcl-2, Bax, caspase-3 and p-53 genes involved in apoptosis and the development of bortezomib-resistance in MM cell lines. Materials and methods Multiple myeloma KMS20 (bortezomib-resistant) and KMS28 (bortezomib-sensitive) cell lines were used. 3-[4,5-Dimethylthiazol-2-yl] 1-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine IC50 values of bortezomib. RNAs were isolated from bortezomib-treated cell lines, followed by cDNA synthesis. Expression levels of the genes were analyzed by using q-Realtime-PCR. Results As a result, Bcl-2/Bax ratio was higher in KMS20 (resistant) cells than in KMS28 (sensitive) cells. Expression of caspase-3 decreased in KMS20-cells, whereas increased in KMS28-cells. The results indicate that apoptosis was suppressed in resistant cells. Conclusion These findings will enable us to understand the molecular mechanisms leading to drug-resistance in MM cells and to develop new methods to prevent the resistance. Consequently, preventing the development of bortezomib resistance by eliminating the factors which suppress apoptosis may be a new hope for MM treatment.
Highlights
Multiple myeloma (MM), the second most common type of hematologic cancer in the world, is characterized by the accumulation of monoclonal B cell-derived malignant plasma cells in the bone marrow [1,2,3]
MM is a malignant plasma cell disorder characterized by the accumulation of tumor cells in the bone marrow [26]
It has been observed that MM patients developed resistance to bortezomib during the course of treatment
Summary
Multiple myeloma (MM), the second most common type of hematologic cancer in the world, is characterized by the accumulation of monoclonal B cell-derived malignant plasma cells in the bone marrow [1,2,3]. The proteasome complex is responsible for the degradation of regulatory proteins involved in pathways such as cell cycle, apoptosis and DNA repair, which are of crucial importance for the survival of the cell [7]. In this system, disruption of proteasome functions leads to see above growth arrest, induction of apoptosis, and as a result cell death [8]. Expression levels of the genes were analyzed by using q-Realtime-PCR
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