mTOR信号通路影响人早幼粒白血病细胞株HL60的趋电性

mTOR signaling pathway affects the electrotaxis of human promyelocytic leukemia cell line HL60

生物电信号指导的细胞定向迁移行为在多细胞生物体的重大生理和病理过程中发挥重要作用,然而电信号指导细胞定向迁移的机制并不清楚.利用体外直流电刺激探究细胞定向迁移机制是研究生物电信号指导细胞行为常用的手段.作者对人早幼粒白血病细胞株HL60的趋电性作用进行了研究,发现在300 mV/mm的直流电场中,HL60细胞发生明显朝向电场阴极的趋电性运动,其趋电性指数和轨迹速度分别为0.89±0.04和9.72±0.38μm/min;Rictor敲低突变株的趋电性与野生型之间无限制性差异.利用高浓度mTOR的特异性抑制剂PP242药物处理HL60细胞后,细胞在直流电场中的趋电性指数降低到0.82±0.06,运动速度也被显著抑制.以上研究结果表明,mTOR信号通路在HL60细胞的趋电性运动中发挥了一定的作用,但Rictor并不是关键基因.研究结果为开发生物电场依赖的靶向药物提供了理论基础.

The directional migration of cells guided by bioelectrical signals plays an important role in the major physiological and pathological processes of multicellular organisms.However,the mechanism of this is not clear.Using in vitro direct current stimulation to explore the mechanism of cell directional migration is a common method to study the bioelectrical signal to guide cell behavior.The effect of mTOR signaling pathway on the electrotaxis of human promyelocytic leukemia cell line HL60 was studied in this paper.The results showed that in a DC electric field of 300 mV/mm,HL60 cells showed obvious electrotaxis towards the cathode of the electric field,and the electrotaxis index and trajectory velocity were 0.89±0.04 and 9.72±0.38μm/min,respectively.There was no restrictive difference between the electrotaxis of Rictor knockdown mutant and wild type.However,after HL60 cells were treated with high concentration of mTOR specific inhibitor PP242,the electrotaxis index of cells in DC electric field decreased to 0.82±0.06,and the movement speed was also significantly inhibited.These results suggest that mTOR signaling pathway plays a role in the electrotaxis of HL60 cells,but Rictor is not a key gene.This result provides a theoretical basis for the development of bioelectric field-dependent targeted drugs.