Evaluation of the Antitumoral Effect of PI3K/AKT/mTOR Pathway Inhibition and Antioxidant Combination on Burkitt Lymphoma Cell Line.

IF 2.3 4区 医学 Q3 ONCOLOGY
Ibrahim Karaduman, Hatice Terzi, Seyma Tastemur, Mehmet Şencan
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引用次数: 0

Abstract

Background and aim: Burkitt lymphoma is a highly aggressive type of B-cell non-Hodgkin lymphoma. While it is more commonly seen in children and adolescents, it accounts for about 1-2% of adult lymphomas. Since it has high Ki-67 ratios, both its progression rate and sensitivity to chemotherapy are high. However, treatment success decreases in chemotherapy-resistant relapsed/refractory groups. Therefore, new and less toxic therapeutic agents targeting biological pathways related to Burkitt lymphoma pathogenesis are needed. In our study, we aimed to determine the antitumoral efficacy of PI3K/AKT/mTOR pathway inhibitor ETP 45658 and antioxidant Resveratrol, which play a role in Burkitt lymphoma pathogenesis on a Burkitt lymphoma cell line.

Methods: Burkitt lymphoma Raji cell line was used in our study. ETP 45658 was applied to the cell line at concentrations of 50, 25, 12.5, 1, 0.1, and 0.01 μM, both alone and in combination with 100 μM resveratrol. The cytotoxic effects of ETP 45658 and the combination treatment on Raji cells were then evaluated using an in vitro XTT cell viability test. IC50 value was calculated according to the results obtained in the XTT test. Based on the IC50 value, the apoptosis assay was studied using the flow cytometry method.

Results: Our research showed that increasing doses of ETP 45658, individually and in combination, had a statistically significant cytotoxic effect on Burkitt lymphoma Raji cells. This cytotoxic effect was found to be higher in combination treatment. In apoptosis experiments with the calculated IC50 value, it induced apoptosis weakly.

Conclusion: Our study showed that ETP 45668 alone and in combination with resveratrol has antitumoral activity on the Burkitt lymphoma cell line. PI3K/Akt/mTOR pathway inhibitors may be an alternative treatment option in patients with relapsed/refractory Burkitt lymphoma. However, more preclinical and clinical studies are needed.

PI3K/AKT/mTOR通路抑制及抗氧化联合对Burkitt淋巴瘤细胞的抗肿瘤作用
背景和目的:伯基特淋巴瘤是一种高度侵袭性的b细胞非霍奇金淋巴瘤。虽然它更常见于儿童和青少年,但它约占成人淋巴瘤的1-2%。由于Ki-67比率高,其进展率和对化疗的敏感性都很高。然而,化疗耐药复发/难治性组的治疗成功率降低。因此,需要针对与伯基特淋巴瘤发病机制相关的生物学途径开发新的毒性较小的治疗药物。在我们的研究中,我们旨在确定PI3K/AKT/mTOR通路抑制剂ETP 45658和抗氧化剂白藜芦醇在Burkitt淋巴瘤细胞系上的抗肿瘤功效,这两种物质在Burkitt淋巴瘤的发病过程中起作用。方法:采用伯基特淋巴瘤Raji细胞系进行研究。ETP 45658分别在50、25、12.5、1、0.1和0.01 μM浓度下作用于细胞系,单独作用或与100 μM白藜芦醇联合作用。采用体外XTT细胞活力试验评价ETP 45658及联合处理对Raji细胞的细胞毒作用。根据XTT试验结果计算IC50值。根据IC50值,采用流式细胞术进行细胞凋亡检测。结果:我们的研究表明,增加ETP 45658剂量,单独和联合使用,对伯基特淋巴瘤Raji细胞具有统计学上显著的细胞毒作用。这种细胞毒性作用在联合治疗中被发现更高。在计算IC50值的细胞凋亡实验中,它对细胞凋亡的诱导作用较弱。结论:本研究表明,ETP 45668单独或联合白藜芦醇对伯基特淋巴瘤细胞系具有抗肿瘤活性。PI3K/Akt/mTOR通路抑制剂可能是复发/难治性伯基特淋巴瘤患者的替代治疗选择。然而,需要更多的临床前和临床研究。
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来源期刊
Current cancer drug targets
Current cancer drug targets 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
105
审稿时长
1 months
期刊介绍: Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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