白藜芦醇抑制荷骨肉瘤小鼠肿瘤生长的机制研究

Resveratrol inhibits growth of osteosarcoma transplanted in mice

目的:探讨白藜芦醇(RES)抗荷骨肉瘤小鼠移植瘤生长的作用及其机制。方法:构建小鼠移植瘤模型,RES注射给药,每日观察体重及瘤体变化,RT-qPCR检测肿瘤细胞Xiap、Kras、Mcl-1、Bcl-2、CyclinE1、BAX基因的表达,Western blot检测相应蛋白表达;流式细胞术检测体内外肿瘤细胞PD-L1表达,以及移植瘤组织中CD8+T细胞、NK细胞、NKT细胞、MDSCs和Treg细胞数量。结果:RES能抑制小鼠移植瘤生长;在体外增强而在体内降低了肿瘤细胞表面PD-L1表达;下调肿瘤细胞Xiap、Kras、Mcl-1、Bcl-2、CyclinE1 mRNA及相应蛋白的表达,提高BAX mRNA及相应蛋白表达水平;增加肿瘤组织中CD8+T细胞、NK细胞、NKT细胞百分比,降低MDSCs和Treg细胞百分比。结论:RES能显著抑制荷骨肉瘤小鼠移植瘤生长,其机制与调控细胞凋亡和细胞周期相关基因和蛋白表达有关;同时,RES能调节移植瘤中多种免疫细胞发挥抗肿瘤效应。

Objective:To investigate the mechanism involved in the effect of resveratrol(RES) on inhibiting the growth of osteosarcoma.Methods:Osteosarcoma transplanted mice model was constructed and treated with RES at different doses, the body weight and tumor volume of the mice were recorded daily.The gene expression of Xiap, Kras, Mcl-1,Bcl-2,CyclinE1 and BAX in tumor cells were detected by RT-qPCR and the expression of the corresponding proteins were checked by Western blot.The expression of PD-L1 on tumor cells in vitro and in vivo and the percentages of CD8+T cells, NK cells, NKT cells, MDSCs and Treg cells infiltrating in transplanted tumor tissues were measured by flow cytometry.Results:RES inhibited the growth of osteosarcoma transplanted in mice.RES enhanced the expression of PD-L1 in vitro and down-regulated it in vivo.RES treatment decreased the mRNAs and corresponding proteins expression levels of XIAP,Kras, Mcl-1,Bcl-2,CyclinE1.On the other hand, RES treatment enhanced that expression of BAX in tumor cells.RES treatment increased the percentages of CD8+T cells, NK cells, NKT cells and decreased the percentages of MDSCs and Treg cells in tumor tissues.Conclusion:RES has the potential to inhibited the growth of osteosarcoma transplanted in K7 M2 mice.The mechanism is related to regulating the apoptosis and cell cycle-related genes and proteins expression.At the same time, RES regulates various immune cells to exert anti-tumor effects.