RESUMEN
Background and Aim: Since proteasome is strongly considered to be involved in the development and progression of a wide variety of hematological malignancies in particular, multiple myeloma, blockage of this hemostasis system with different types of proteasome inhibitors seems to be a promising way of treatment for multiple myeloma. In this study, we investigated the effect of Kyprolis, a new irreversible proteasome inhibitor [PI], on the survival rate of multiple myeloma -derived KMM-1 cell line
Material and Methods: To evaluate whether inhibition of proteasome using Kyprolis could exert cytotoxic effect in multiple myeloma, KMM-1 cells were cultured with different concentrations [25-150 nM] of the inhibitor for 24 and 48 hours. Then trypan blue exclusion assay, MTT assay, flocytometric cell cycle analysis were performed and we evaluated gene expression changes associated with apoptosis
Results: The results of this study demonstrated that Kyprolis induced both cytotoxic and anti- proliferative effects on KMM-1 cells. This inhibitor is able to reduce the cell survival and metabolic activity in a dose- and also time-dependent manner [p = 0.001]. Moreover, we found that Kyprolis increased cell population in G1 phase of cell cycle to 52.33% probably through up-regulation of p73 gene expression [p = 0.05]. Exposing multiple myeloma cells to this proteasome inhibitor also led to induction of apoptosis probably through alterations in the gene expression of pro- and anti-apoptotic related genes [p = 0.05]
Conclusions: The results of this study clearly indicated that Kyprolis had anti-tumor activity against KMM-1 cells