联合应用活性氧抑制剂对降低胃癌顺铂耐药性的影响

ROS inhibitor reduces resistance of gastric cancer cells to cisplatin

目的探讨活性氧抑制剂N-乙酰半胱氨酸(NAC)通过Akt(蛋白激酶B)有关的信号途径在胃癌细胞中对顺铂化疗敏感性的影响。方法应用化疗药物顺铂以一系列梯度浓度处理对数期生长的胃癌BGC-823细胞,通过MIT法检测顺铂对BGC-823细胞增殖抑制率的影响,应用顺铂和活性氧抑制剂NAC单独及联合应用处理胃癌BGC细胞后测定细胞的活性氧水平以及Akt及磷酸化Akt的表达水平。结果顺铂对胃癌细胞有明显的抑制作用,呈浓度依赖性。单用顺铂组活性氧水平高于联合用药组;顺铂联合应用活性氧抑制剂NAC组与单用顺铂或活性氧抑制剂组的Akt表达无统计学意义(P>0.05),而磷酸化Akt的表达下调(P<0.05)。结论活性氧抑制剂NAC可能通过阻断P13K/Akt信号途径或其他有关Akt的信号通路以提高癌细胞对顺铂化疗的敏感性。

Objective To investigate whether NAC, a ROS inhibitor, reduces resistance of gastric cancer cell line BGC-823 to cisplatin and to explore possible mechanisms. Methods The growth inhibition effect of cisplatin in 24 h on human gastric cancer cell line BGC-823 was detected by MTT; cisplatin alone or combination with NAC was used to treat subcuhured BGC-823 cells. After treatment, the level of ROS was determined by reactive oxygen species assay kit and Akt and p-Akt expression was detected by Western blotting. Results Cisplatin could inhibit the growth and promote the apoptosis of human gastric cancer BCC-823 cells. The level of ROS was higher in the cisplatin group. Expression of Akt showed no significant difference between cells treated with cisplatin alone and those treated with combined cisplatin and NAC, while the phosphorylation of Akt was significantly lower in the combination group than that in the cisplatin group. Conclusion The ROS inhibitor NAC could block the Akt signaling pathways and increase the sensitivity of gastric cells to eisplatin.