评估 PI3K/AKT/MTOR 通路抑制剂奥米帕利对伯基特淋巴瘤细胞系的抗肿瘤活性

Zekeriya Keski̇n, Fatih Yulak, Hatice Terzi̇, M. İnanir
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摘要

伯基特淋巴瘤的治疗面临许多挑战,尤其是免疫力低下者、老年患者以及复发或难治患者。因此,需要新的、毒性较低的治疗药物。本研究旨在确定 PI3K/AKT/mTOR 通路抑制剂奥米帕利在伯基特淋巴瘤中的抗肿瘤活性。研究使用了 Raji 细胞系。给细胞系注射奥米帕利,然后通过 XTT 试验评估奥米帕利对 Raji 细胞的细胞毒性作用。根据 XTT 试验结果计算 IC50 值。根据计算出的 IC50 值进行细胞凋亡和细胞周期实验。采用流式细胞计数法确定奥米帕利对细胞凋亡和细胞死亡的影响。研究结果表明,浓度不断增加的奥米帕利对 Raji 细胞的细胞毒性作用具有统计学意义。凋亡实验显示,奥米帕利司能强烈诱导细胞凋亡。细胞周期实验表明,奥米帕利西促细胞周期停滞在 G0/G1 期。结论是奥米帕利对伯基特淋巴瘤细胞具有抗肿瘤活性,其细胞毒性作用可诱导细胞凋亡和细胞周期停滞。考虑到这一效应,用奥米帕利来靶向 PI3K/AKT/mTOR 通路可能是一种新的治疗选择。
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Evaluation of the Antitumor Activity of Omipalisib, a PI3K/AKT/MTOR Pathway Inhibitor, on Burkitt Lymphoma Cell Line
There are many challenges in the treatment of Burkitt lymphoma, especially in immunocompromised individuals, elderly patients, and patients with relapsed or refractory disease. Therefore, there is a need for new and less toxic therapeutic agents. The aim of this study was to determine the antitumoral activity of omipalisib, a PI3K/AKT/mTOR pathway inhibitor, in the Burkitt lymphoma. Raji cell line was used in the study. Omipalisib was administered to the cell line and then the cytotoxic effect of omipalisib on Raji cells was evaluated by the XTT test. The IC50 value was calculated according to the results of the XTT test. Apoptosis and cell cycle experiments were studied with the calculated IC50 value. The flow cytometric method was used to determine the effect of omipalisib on apoptosis and cell death. The results of the study showed a statistically significant cytotoxic effect of increasing concentrations of omipalisib on Raji cells. The apoptosis experiment performed revealed that omipalisib strongly induced apoptosis. The cell cycle experiment showed that omipalisib stimulated the cell cycle arrest at the G0/G1 phase. It was concluded that omipalisib exhibited antitumoral activity on Burkitt lymphoma cells with its cytotoxic effect and induced apoptosis and cell cycle arrest. Considering this effect, targeting the PI3K/AKT/mTOR pathway with omipalisib can be a new treatment option.
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