三硫二苄基通过抑制JAK/STAT3信号通路抑制A549细胞的增殖和转移  

Dibenzyl trisulfide inhibits the proliferation and metastasis of A549 cell via suppressing JAK/STAT3 signal pathway

作　　者：张路 高二可 金齐力[1] 韩晓静 钱峰[1] ZHANG Lu;GAO Erke;JIN Qili;HAN Xiaojing;QIAN Feng(Bengbu Medical College,Bengbu,Anhui 233004,China)

机构地区：[1]蚌埠医学院,安徽蚌埠233004

出　　处：《石河子大学学报（自然科学版）》2022年第4期421-430,共10页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(81973329);安徽省重点研究与开发计划项目(202104j07020021)。

摘　　要：目的探讨三硫二苄基(DTS)对非小细胞肺癌(NSCLC)细胞系A549细胞增殖、转移和侵袭的抑制作用及其机制。方法克隆形成和CCK-8检测DTS对A549细胞增殖的影响;Annexin V-FITC/PI双染色法与免疫印迹检测DTS对A549细胞凋亡及凋亡相关蛋白Bax,Bcl-2表达的影响;划痕实验和Transwell侵袭实验检测DTS对A549细胞迁移和侵袭的影响;免疫印迹检测DTS对A549细胞上皮间质转化(EMT)和JAK/STAT3信号通路相关蛋白表达的影响;利用IL-6可以激活STAT3信号通路,利用划痕实验,Transwell侵袭实验和Western blot免疫印迹分析验证DTS对A549细胞增殖和转移的作用依赖JAK/STAT3信号通路。结果我们的结果显示DTS能抑制A549细胞增殖、迁移、侵袭并诱导其凋亡;DTS诱导促凋亡基因Bax的表达,降低抗凋亡基因Bcl-2的表达;DTS减弱EMT转化,且与JAK和STAT3磷酸化相关;IL-6通过激活STAT3信号通路可以挽救A549细胞的迁移能力。结论DTS具有干预JAK/STAT3信号通路,从而抑制A549细胞增殖,促进细胞凋亡,抑制细胞迁移和侵袭的生物学作用。因此,DTS可能成为潜在治疗NSCLC的药物。Objective To determine the effect of dibenzyl trisulfide(DTS)on the proliferation and metastasis of NSCLC cell line A549 cell and its related mechanisms.Methods The effect of DTS on the proliferation of A549 cell was detected by colony formation assay and CCK-8 assay,which was also proved by Annexin V-FITC/PI double staining and Western blot.The effect of DTS on apoptosis and apoptosis-related proteins Bax and Bcl-2 was also detected.And the wound healing assay and Transwell assay were used to determine the effects of DTS on the migration of A549 cell.Then,the effect of DTS on EMT and JAK/STAT3 signaling pathway-related protein expression was detected by Western blot assay.In response to IL-6 treatment,the effect of DTS on the proliferation and metastasis of A549 cell was determined.Results Our results showed that DTS significantly inhibited the proliferation and migration of A549 cell,as well as induced apoptosis.Meanwhile,DTS increased the expression of the pro-apoptotic gene Bax and decreased the expression of the anti-apoptotic gene Bcl-2.Meanwhile,DTS treatment attenuated EMT,which was associated with inhibition of JAK,STAT3 phosphorylation.Furthermore,IL-6 treatment induced STAT3 phosphorylation and rescued the migration and invasion of A549 cell.Conclusions DTS has effects on inhibition of A549 cell proliferation and migration,and induction of its apoptosis.Additionally,DTS inhibited A549 EMT by reducing JAK/STAT3 signaling.

关 键 词：三硫二苄基 非小细胞肺癌 转移 上皮间质转化 JAK/STAT3 

分 类 号：R734[医药卫生—肿瘤]