Evaluation of BAX and BCL-2 Gene Expression and Apoptosis Induction in Acute Lymphoblastic Leukemia Cell Line CCRFCEM after High- Dose Prednisolone Treatment

Abstract

Objective: Glucocorticoids are one of the most important drugs in the treatment of acute lymphoblastic leukemia<br />for children. It is very important to response to glucocorticoid in the prognosis of these patients. Therefore, resistance<br />to treatment is a major problem in lymphoid leukemia cases. In, this study, CCRF-CEM cell line was selected as a<br />chemotherapy-resistant model. The aim of this study was to evaluate the effect of high dose prednisolone on induction<br />of apoptosis and changes in BAX and BCL-2 gene expression at different times. Methods: CCRF-CEM cell lines were<br />grown in standard conditions. Based on previous studies, a dose of 700 μM as subtoxic dose was selected. Changes in<br />gene expression of BAX and BCL-2 were evaluated by using real time PCR techniques. Also stained with annexin V<br />and the induction of apoptosis was assessed by FACS machine. Results: In this study it was found that prednisolone in<br />high doses at different times significantly increased the gene expression of BAX and on the other hand the amount of<br />BCL-2 expression was reduced. Cells that treated for 48 hours had more significant changes in gene expression. Based<br />on flowcytometry data, prednisolone can induce apoptosis in a time dependent manner on this cancerous resistant cell<br />line. Conclusions: Apoptosis induced by high-dose prednisolone in the CCRF-CEM cells, which is almost resistant,<br />and possibly mediated by reducing the expression of BCL-2 and BAX up-regulation.