SAPK/JNK信号通路在二甲双胍和达卡巴嗪协同诱导Raji和Ramos淋巴瘤细胞凋亡中的作用
The Role of SAPK/JNK Pathway in the Synergistic Effects of Metformin and Dacarbazine on Apoptosis in Raji and Ramos Lymphoma Cells.
作者信息
Naserian Maryam, Ramazani Elham, Iranshahi Mehrdad, Tayarani-Najaran Zahra
机构信息
Department of Biology, Faculty of Science, Hakim Sabzevari University, Sabzevar, Iran.
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
出版信息
Curr Mol Pharmacol. 2018;11(4):336-342. doi: 10.2174/1874467211666180830150546.
BACKGROUND
Besides the first-line medication for the treatment of type 2 diabetes, the growth inhibitory activity of metformin alone or in combination with conventional chemotherapeutics has been addressed on a panel of cell lines. In this study, we investigated the cytotoxicity and apoptosis of the metformin alone and in combination with dacarbazine in Raji and Ramos lymphoma cell lines.
METHODS
Cell viability and apoptosis measured using resazurin assay, flow cytometry of PI stained cells and western blot analysis.
RESULTS
Metformin showed synergistic cytotoxic effects in combination with dacarbazine, reduced cell viability, and increased apoptosis in Raji and Ramos lymphoma cells in comparison with the use of each drug alone. The activation of MAPK and SAPK/JNK (P-SAPK/JNK) were shown in both cells.
CONCLUSION
Overall, the result verified the synergistic effect of the metformin-dacarbazine combination, which has the value in reducing the chemotherapeutic agent dose, adverse effect and the burden of treatment for the community and patients.
背景
除了用于治疗2型糖尿病的一线药物外，二甲双胍单独或与传统化疗药物联合使用时对一组细胞系的生长抑制活性已得到研究。在本研究中，我们调查了二甲双胍单独及与达卡巴嗪联合使用对Raji和Ramos淋巴瘤细胞系的细胞毒性和凋亡情况。
方法
使用刃天青检测法、PI染色细胞的流式细胞术和蛋白质印迹分析来测定细胞活力和凋亡情况。
结果
与单独使用每种药物相比，二甲双胍与达卡巴嗪联合使用时在Raji和Ramos淋巴瘤细胞中显示出协同细胞毒性作用，降低了细胞活力，并增加了凋亡。两种细胞中均显示出MAPK和SAPK/JNK（磷酸化SAPK/JNK）的激活。
结论
总体而言，结果证实了二甲双胍-达卡巴嗪联合使用的协同作用，这对于减少化疗药物剂量、不良反应以及减轻社区和患者的治疗负担具有价值。
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