Bcl-2抑制剂S1通过内质网途径对小鼠黑色素瘤B16细胞移植瘤生长抑制作用

摘要

目的：建立小鼠黑色素瘤B16细胞移植瘤模型，探讨 Bcl-2抑制剂 S1对其生长的影响及其作用机制。方法将小鼠黑色素瘤B16细胞种植至小鼠腋下，14天后开始用药物治疗，隔天给药。实验分为对照组、S1组（0．6 mg／kg），28天后处死。测量移植瘤的重量。并采用免疫组化法检测内质网应激、凋亡相关蛋白等蛋白表达水平的变化。结果与对照组相比，S1处理组能够明显降低移植瘤体积、重量，差异有统计学意义（P＜0．05）；应用 S1后移植瘤中Caspase3表达增加、抗凋亡蛋白 Bcl-2表达减少、内质网应激相关蛋白 GRP78以及内质网应激-凋亡相关蛋白CHOP表达水平明显上升，差异有统计学意义（P＜0．05）。结论小分子化合物 S1可以抑制小鼠黑色素瘤 B16细胞移植瘤的生长，其作用途径可能同内质网凋亡信号通路相关。%Objective This study was to establish tranplanted mouse melanoma models and investigate the inhibitory effects of Bcl-2 inhibitor S1 on them.Methods Mouse melanoma B1 6 cells were implanted into the mice under the arm-pit.The mice were treated with S1 every two days after 14 days,and were killed 28 days latter.Tumor volume and weight were measured.The experssion of proteins involed in Endoplasmic Reticulum Stress(ERS)and apoptosis were observed by immunohistochemistry.Results Compared with the control group,the average tumor volume was smaller and the average tumor weight were lighter in S1 group;the average experssion of Capase3 was higher,the experssion of Bcl-2 was lower,the experssion of proteins relating with ERS-GRP78 and CHOP were higher.Conclusion S1 inhibits the growth of B1 6 cells xenografts in mice,ERS may be related to the process.