Renieramycin T通过Nrf2-STAT3信号通路抑制结直肠癌细胞的迁移和侵袭  

Renieramycin T inhibition of CRC cell migration and invasion via Nrf2-STAT3 signaling pathway

作　　者：张长悦 梁敬 陈瑞蛟[2] ZHANG Changyue;LIANG Jing;CHEN Ruijiao(School of Pharmacy,Binzhou Medical University,Yantai 264003,China;School of Medical Imaging and Laboratory,Jining Medical University,Jining 272067,China)

机构地区：[1]滨州医学院药学院,烟台264003 [2]济宁医学院医学影像与检验学院,济宁272067

出　　处：《济宁医学院学报》2025年第2期97-103,共7页Journal of Jining Medical University

基　　金：济宁医学院贺林院士新医学临床转化工作站科研基金(JYHL2022ZD04)。

摘　　要：目的本研究旨在探究Renieramycin T(RT)对结直肠癌(colorectal cancer,CRC)的作用,并初步揭示其发挥抑制作用的分子机制。方法利用THP-1细胞的上清液与HCT116细胞进行条件培养,模拟肿瘤微环境。实验分组为对照组、THP-1与HCT116细胞的共培养组(CM组)、CM+RT 20nM组、CM+RT 80nM组。用RT处理HCT116细胞,CCK-8实验检测细胞活性变化。细胞划痕实验检测细胞迁移能力变化,Transwell实验检测细胞侵袭能力变化,Western blotting实验探索其分子机制。结果RT能以浓度依赖性的方式抑制肿瘤微环境下的HCT116细胞的迁移和侵袭。细胞划痕实验表明,与对照组相比,在肿瘤微环境下CM组HCT116细胞迁移能力增强,而添加RT处理后,CM+RT 20nM组和CM+RT 80nM组HCT116细胞的迁移能力减弱(P<0.05);在Transwell实验中也得到了相同的结果,在肿瘤微环境下HCT116细胞侵袭的促进作用在RT处理后被部分减弱(P<0.05);Western blotting结果显示,在肿瘤微环境下STAT3、p-STAT3和Nrf2蛋白水平的表达明显增加,而RT可部分抑制STAT3、p-STAT3和Nrf2蛋白的表达,RT可抑制磷酸化STAT3和Nrf2的表达(P<0.05)。结论RT可通过调控Nrf2-STAT3信号通路抑制CRC细胞迁移和侵袭,可能成为治疗转移性CRC的潜在新型药物。Objective To investigate the anti-colorectal cancer activity of RT and to reveal the molecular mechanism by which it exerts its inhibitory effect.Methods A tumor microenvironment was simulated by co-culture of supernatants of THP-1 cells with HCT116 cells.The experimental groups were control group,co-culture(CM)of THP-1 and HCT116 cells,CM+RT20nM,CM+RT80nM.The HCT116 cells were then treated with RT.CCK-8 assay was used to detect the changes in cell activity,cell migration was detected by cell scratch assay,cell invasion was detected by Trans-well assay,and the molecular mechanism was verified by Western blotting.Results RT inhibited the migration and invasion of HCT116 cells in the tumour microenvironment in a concentration-dependent manner.The cell scratch assay showed that the migration ability of HCT116 in the CM group was enhanced in the tumour microenvironment compared with the control group,while it was weakened by the addition of RT treatment(P<0.0001);the same results were obtained in the Transwell assay,which showed that the promotion of HCT116 invasion in the tumour microenvironment was partially attenuated by RT treatment(P<0.05);furthermore,Western blotting results showed that the expression of STAT3,p-STAT3 and Nrf2 protein levels were obvious in the tumour microenvironment,while RT treatment partially in hibited the expression of STAT3,p-STAT3 and Nrf2 proteins,and RT inhibited the expression of phosphorylated STAT3 and Nrf2(P<0.05).Conclusion RT inhibits CRC cell metastasis through Nrf2-STAT3 signaling.This may be a novel drug for the treatment of metastatic colon cancer.

关 键 词：Renieramycin T 结直肠癌 肿瘤迁移与侵袭 P-STAT3 NRF2 

分 类 号：R96[医药卫生—药理学]