Ghasemi Amin, Khanzadeh Taghi, Zadi Heydarabad Milad, Khorrami Arash, Jahanban Esfahlan Akram, Ghavipanjeh Somayeh, Gholipour Belverdi Mahdi, Darvishani Fikouhi Saghar, Darbin Akbar, Najafpour Malihe, Azimi Ako
Student Research Committee, Maragheh University of Medical Sciences, Maragheh, Iran. Email:
Asian Pac J Cancer Prev. 2018 Aug 24;19(8):2319-2323. doi: 10.22034/APJCP.2018.19.8.2319.
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.
糖皮质激素是治疗儿童急性淋巴细胞白血病最重要的药物之一。这些患者对糖皮质激素的反应在预后中非常重要。因此，治疗耐药是淋巴白血病病例中的一个主要问题。在本研究中，选择CCRF-CEM细胞系作为化疗耐药模型。本研究的目的是评估高剂量泼尼松龙在不同时间对细胞凋亡诱导的影响以及BAX和BCL-2基因表达的变化。方法：CCRF-CEM细胞系在标准条件下培养。根据先前的研究，选择700μM作为亚毒性剂量。通过实时PCR技术评估BAX和BCL-2的基因表达变化。还用膜联蛋白V染色，并通过流式细胞仪评估细胞凋亡的诱导情况。结果：在本研究中发现，不同时间的高剂量泼尼松龙显著增加了BAX的基因表达，另一方面BCL-2的表达量降低。处理48小时的细胞在基因表达上有更显著的变化。根据流式细胞术数据，泼尼松龙可在这种癌性耐药细胞系上以时间依赖性方式诱导细胞凋亡。结论：高剂量泼尼松龙在几乎耐药的CCRF-CEM细胞中诱导细胞凋亡，可能是通过降低BCL-2的表达和上调BAX介导的。
