山椒子烯酮通过调控PI3K/AKT介导的肿瘤相关巨噬细胞极化影响结直肠癌进展  

Zeylenone affects colorectal cancer progression by regulating PI3K/AKTmediated polarization of tumor-associated macrophages

作　　者：李登云 王涛丽 岳丽晓 赵新永 王世广 LI Dengyun;WANG Taoli;YUE Lixiao;ZHAO Xinyong;WANG Shiguang(Medical College,Zhengzhou University of Industrial Technology,Xinzheng 451100,China)

机构地区：[1]郑州工业应用技术学院医学院,新郑451100

出　　处：《中国免疫学杂志》2024年第5期970-976,共7页Chinese Journal of Immunology

基　　金：河南省社发领域科技攻关项目(192102310442);校级一般科研项目(2023YB040)。

摘　　要：目的:分析山椒子烯酮在结直肠癌中的抗肿瘤活性及其相关调节机制。方法:用不同浓度的山椒子烯酮(0、2.5、5、10、20μmol/L)处理人结直肠癌细胞(DLD-1与HCT116)和对照细胞(HcoEpic)48 h。CCK-8试剂盒测定DLD-1、HCT116和HcoEpic的细胞活性;TUNEL试剂盒检测细胞凋亡;ELISA测定caspase-3的活性与LDH水平;Western blot与qRT-PCR检测M1与M2极化标志物、p-PI3K/PI3K与p-AKT/AKT的相对表达水平。将DLD-1细胞皮下注射于裸鼠腋下构建小鼠移植瘤模型。山椒子烯酮裸鼠腹腔注射剂量为30 mg/kg,1次/2 d。2周后检测山椒子烯酮对结直肠癌肿瘤生长的影响。结果:山椒子烯酮抑制结直肠癌细胞活性,促进结直肠癌细胞凋亡。山椒子烯酮促进结直肠癌中巨噬细胞M1极化,抑制M2极化(P<0.05)。山椒子烯酮抑制结直肠癌细胞PI3K/AKT信号通路(P<0.05)。PI3K/AKT信号通路激活剂(740 Y-P)减弱了山椒子烯酮对结直肠癌细胞的影响。在小鼠移植瘤模型中,山椒子烯酮抑制结直肠癌肿瘤生长(P<0.05)。结论:山椒子烯酮通过调控PI3K/AKT信号通路抑制结直肠癌细胞活性,促进结直肠癌细胞凋亡和巨噬细胞M1极化,最终抑制结直肠癌进展。Objective:To study the antitumor activity of zeylenone in colorectal cancer and its related regulatory mechanism.Methods:Human colorectal cancer cells(DLD-1 and HCT116)and control cell(HcoEpic)were treated with different concentrations of zeylenone(0,2.5,5,10 and 20μmol/L)for 48 h.Cell viability of DLD-1,HCT116 and HcoEpic were determined by CCK-8 kit.TUNEL staining was used to evaluate cell apoptosis.Caspase-3 activity and LDH level were measured by ELISA.Relative levels of M1 and M2 polarization markers,p-PI3K/PI3K and p-AKT/AKT were detected by Western blot and qRT-PCR.DLD-1 cells were subcutaneously injected into the armpit of nude mice to establish a mouse xenograft tumor model.Intraperitoneal dose of zeylenone given to nude mice was 30 mg/kg,administered once every two days.After 2 weeks,the effect of zeylenone on growth of colorectal cancer tumors was detected.Results:Zeylenone inhibited cell activity and promoted cell apoptosis in colorectal cancer cells.Additionally,zeylenone stimulated M1-polarization and inhibited M2-polarization of tumor-associated macrophages(P<0.05).PI3K/AKT signaling pathway was inhibited by zeylenone in colorectal cancer cells(P<0.05).PI3K/AKT signaling pathway activator(740 Y-P)attenuated the effect of zeylenone on colorectal cancer cells.In mouse xenograft model,zeylenone inhibited the growth of colorectal cancer tumors(P<0.05).Conclusion:Zeylenone can inhibit colorectal cancer cell activity,promote colorectal cancer cell apoptosis,and promote M1 polarization of tumor-associated macrophages by regulating PI3K/AKT signaling pathway,ultimately inhibiting the progression of colorectal cancer.

关 键 词：山椒子烯酮 结直肠癌 PI3K/AKT信号通路 巨噬细胞 

分 类 号：R735.3[医药卫生—肿瘤]