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目的探讨MG132对人类肿瘤细胞U2OS、HepG2和MCF7的生长抑制作用及机制。方法 MTS法检测MG132对肿瘤细胞生长的影响;化学/荧光发光法检测MG132对细胞内O2-及ROS含量的影响;谷胱甘肽检测试剂盒检测细胞内GSH水平变化;Western blot检测MG132对核转录因子Nrf2及γ-谷氨酰半胱氨酸合成酶γ-GCS表达的影响,探索MG132的抗肿瘤作用机制。结果 MG132可剂量依赖性地抑制U2OS、HepG2和MCF7细胞的生长,其IC50值分别为3μM、3μM和2μM;MG132可升高细胞内ROS水平,降低细胞内GSH水平;同时MG132降低了Nrf2及γ-GCS的表达。结论蛋白酶抑制剂MG132对U2OS、HepG2和MCF7细胞的生长具有抑制作用,其可能通过抑制Nrf2及γ-GCS的表达来降低细胞内的GSH水平,从而发挥其抗肿瘤作用。
Objective To investigate the inhibitory effect and mechanism of MG132 on the growth of human tumor cells U2OS, HepG2 and MCF7. Methods The effect of MG132 on the growth of tumor cells was detected by MTS method. The effect of MG132 on the content of O2- and ROS in cells was detected by chemiluminescence / luminescence assay. The change of intracellular GSH level was detected by glutathione assay kit. The transcription factor Nrf2 and γ-glutamylcysteine synthetase γ-GCS expression explore the anti-tumor mechanism of MG132. Results MG132 inhibited the growth of U2OS, HepG2 and MCF7 cells in a dose-dependent manner with IC50 values of 3μM, 3μM and 2μM, respectively. MG132 increased intracellular ROS levels and decreased intracellular GSH levels, while MG132 reduced Nrf2 and γ -GCS expression. Conclusion The protease inhibitor MG132 can inhibit the growth of U2OS, HepG2 and MCF7 cells, which may play an antitumor effect by inhibiting the expression of Nrf2 and γ-GCS to reduce intracellular GSH levels.