مجله علمی دانشگاه علوم پزشکی کردستان (Dec 2019)
Cytotoxic and apoptotic effects of neurokinin-1 receptor (NK1R) antagonist on multiple myeloma cells
Abstract
Background and Aim: Despite therapeutic improvements in recent decades, multiple myeloma (MM) still remains as one of the leading causes of death all over the world. Previous studies have indicated role of neurokinin-1 receptor (NK1R) in the pathogenesis of cancer. Therefore, we decided to evaluate cytotoxic and apoptotic effects of aprepitant (NK1R antagonist) on MM-derived KMM-1 cell line. Material and Method: In this experimental study, for assessment of cytotoxic effect of aprepitant on MM cells, KMM-1 (prepared in Tarbiat Modarres University) were exposed to different concentrations of the inhibitor (5,15, 30 and 45 µM) and subsequently viability, cell count, metabolic activity, and induction of apoptosis were investigated using trypan blue, MTT, and annexin/PI staining assays respectively. Moreover, in order to examine the molecular mechanism of action of aprepitant in KMM-1 cells, gene expression analysis was performed by real-time PCR. Results: The results indicated that NK1R inhibition using aprepitant resulted in considerable growth suppression of KMM-1 cells. Moreover, we found that the cytotoxic effects were likely due to cell arrest in G1 phase and induction of apoptosis, as revealed by the increased percentage of annexin-V/PI double positive cells among the inhibitor-treated cells (P<0.05). Also, RQ-PCR analysis revealed aprepitant changed the ratio of expression of pro apoptotic to anti apoptotic genes by way of alteration in the expression levels of Bax and Bcl-2 (P<0.05). Conclusion: The present study highlighted the efficiency of aprepitant in suppression of the growth of KMM-1 cells; however, further studies are needed to determine the safety and efficacy of this agent for the treatment of MM patients.
