TY - JOUR JF - Koomesh JO - Koomesh VL - 20 IS - 4 PY - 1397 Y1 - 1397/6/01 TI - Induction of p21- and p27-mediated cell cycle arrest in Nalm-6 cells using pan-PI3K inhibitor (Buparlisib) TT - القاء توقف چرخه سلولی در سلول‌های Nalm-6 متعاقب تیمار با مهارکننده تمام ایزوفرومی P‌I3K (Buparlisib) از طریق افزایش بیان p21 و p27 N2 - Introduction: In the era of targeted therapies, efforts are being made to identify the novel agents with strong anti-tumor activity in order to improve cure rates of human malignancies while reducing the toxic side effects of intensive regimens. Increasing number of genetic and cancer biology studies indicated a prominent role for the aberrant activation of PI3K/Akt pathway in not only the pathogenesis of acute lymphoblastic leukemia (ALL), but also in acquisition of chemo-resistant phenotype. In this study we aimed to assess the anti-proliferative effect of pan class I PI3K inhibitor, Buparlisib, on Nalm-6 cells. Materials and Methods: To evaluate whether inhibition of PI3K using Buparlisib could exert anti-proliferative effect in leukemic cells, Nalm-6 were subjected to different concentrations of the inhibitor and subsequent cell viability, cell count, cell cycle progression and transcriptional alteration of cell cycle-related genes were investigated. Results: Buparlisib not only decreased the number of viable inhibitor-treated cells in a concentration and time-dependent manner, but also reduced the survival rate of Nalm-6 cells. Furthermore, we found that the anti-proliferative effect of this inhibitor is mediated, at least partially, through induction of G1 arrest as a result of up-regulated p21 and p27 and down-regulated c.Myc expression level. Conclusion: The present study showed that Buparlisib decreased the proliferative capacity of Nalm-6 cells probably via reduction in DNA synthesize rate, induction of cell cycle arrest and alteration in the expression level of proliferative-related genes. The results suggest that PI3K inhibitors may be used as a promising therapeutic strategy for the treatment of ALL patients. SP - 756 EP - 763 AU - Safaroghli-Azar, A. va AU - Sadri, Mohammadreza AU - Bashash, Davood AD - Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran KW - Cell cycle KW - Acute Lymphoblastic Leukemia KW - PI3K Pathway KW - Buparlisib KW - Nalm-6 UR - http://koomeshjournal.semums.ac.ir/article-1-4410-en.html ER -