Apoptotic Effect of Phosphatidylinositol 3-Kinase Inhibition on Acute Lymphoblastic Leukemia Cells Using Buparlisib

Abstract

BACKGROUND AND OBJECTIVE: Resistance to chemotherapy is one of the most important problems in treatment of patients diagnosed with acute lymphoblastic leukemia (ALL). Pathway interruption of the phosphatidylinositol -3 kinase (PI3K) and its relation to resistance phenomena cause the inhibitors of this pathway, particularly buparlisib are introduced as one of the most promising cancer drugs. The aim of this study was to evaluate the effect of PI3K pathway inhibition on reducing the survival and induction of apoptosis in Nalm-6 cells using buparlisib. METHODS: In this experimental study, the phosphorylation level of Akt was evaluated using western blot to measure the effect of buparlisib on PI3K/Akt pathway in Nalm-6 cells. Nalm-6 cells were treated with different concentrations of buparlisib (0.5-4 µM) for 24, 36 and 48 hours to study the cytotoxic effect of this inhibitor and then, the metabolic activity, induction of apoptosis and changes in expression of genes involved in apoptosis were evaluated using MTT assay, Annexin/PI staining and Rq-PCR, respectively. FINDINGS: Results showed that PI3K pathway inhibition using buparlisib causes the cytotoxic effect on Nalm-6 cells in a dose- and time-dependent manner through reducing p-Akt. These findings suggested that probably, the anti-leukemic effect of buparlisib is mediated through almost 17-fold increase in apoptotic cells (p≤0.001) and rising the mRNA expression level of pro-apoptotic genes (p≤0.01). CONCLUSION: The results indicated that buparlisib has anti-tumor activity against Nalm-6 cells so this inhibitor can be used as a promising agent for the treatment of ALL.