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

Ghasemi, Amin; Khanzadeh, Taghi; Zadi Heydarabad, Milad; Khorrami, Arash; Jahanban Esfahlan, Akram; Ghavipanjeh, Somayeh; Gholipour Belverdi, Mehdi; Darvishani Fikouhi, Saghar; Darbin, Akbar; Najafpour, Malihe; Azimi, Ako

doi:10.22034/APJCP.2018.19.8.2319

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

Document Type : Research Articles

Authors

¹ Student Research Committee, Maragheh University of Medical Sciences, Maragheh, Iran.

² Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

³ Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran.

⁴ Department of Nursing, School of Nursing and Midwifery, Maragheh University of Medical Sciences, Maragheh, Iran.

⁵ Department of Psychiatric Nursing, Maragheh University of Medical Sciences, Maragheh, Iran.

⁶ Shahid Madani Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.

⁷ Medical Biotechnology Research center, School of Nursing, Midwifery and paramedicine, Guilan University of Medical Sciences, Rasht, Iran.

10.22034/APJCP.2018.19.8.2319

Abstract

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

Keywords