ABSTRACT
Background and Aim: In the last decades, experimental studies have shown that aberrant activation of phosphatidylinositol 3-kinase [PI3K] pathway is an essential step for both initiation and maintenance of tumor genesis in a wide range of human cancers, such as, acute promyelocytic leukemia [APL]. In this study, we investigated the cytotoxic effect of BKM120, a pan-PI3K inhibitor, on APL-derived NB4 cells
Material and Methods: To evaluate the inhibitory effect of BKM120 on PI3K/AKt pathway, we analyzed the expression and phosphorylation level of Akt using western blot. Using western blot, phosphorylation rate of Akt was evaluated. In order to evaluate the effect of the inhibitor on the metabolic activity, apoptosis index and alteration of the expression of apoptotic-related genes, we used MTT assay, annexin-V/PI staining and RT-PCR analysis respectively. Using SPSS 17 software data were analyzed by t-test
Results: We found that inhibition of PI3K/Akt pathway by BKM120 resulted in reduction of metabolic activity of APL-derived NB4 cells in a dose- and time-dependent manner [p
Conclusion: BKM-120 exerts a favorable apoptotic effect on NB4 cells through inhibition of the PI3K/Akt signaling pathway
ABSTRACT
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
Conclusions: The results of this study clearly indicated that Kyprolis had anti-tumor activity against KMM-1 cells