西黄胶囊联合西妥昔单抗通过Nrf2/HO-1信号通路调控结直肠癌细胞凋亡、迁移以及侵袭的作用机制研究  

Study on the Mechanism of Apoptosis,Migration,and Invasion Regulation of Colorectal Cancer Cells by Xihuang Capsules Combined with Cetuximab via the Nrf2/HO-1 Signaling Pathway

作　　者：梁亮[1] 李成发 何妍婷 甘芷川 韦维[1] 潘盛 彭雯 黄国东[1] Liang Liang;Li Chengfa;He Yanting;Gan Zhichuan;Wei Wei;Pan Sheng;Peng Wen;Huang Guodong(Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of C)

机构地区：[1]广西中医药大学附属国际壮医医院,南宁530000

出　　处：《成都医学院学报》2024年第4期587-592,共6页Journal of Chengdu Medical College

基　　金：广西高校中青年教师科研基础能力提升项目(No:2021KY0316)。

摘　　要：目的研究西黄胶囊联合西妥昔单抗通过Nrf2/HO-1信号通路对结直肠癌细胞凋亡、迁移以及侵袭的调控作用。方法使用细胞计数试剂盒(CCK8)确定西黄胶囊和西妥昔单抗对结直肠癌HCT-116细胞活力的影响。使用流式细胞术、划痕法和侵袭小室法检测西黄胶囊联合西妥昔单抗对结直肠癌HCT-116细胞凋亡、迁移以及侵袭的影响。使用蛋白质印迹技术检测西黄胶囊联合西妥昔单抗对结直肠癌HCT-116细胞B细胞淋巴瘤2(BCL2)、BCL2关联X蛋白(BAX)、基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)、锌指蛋白232(ZNF320)、血管内皮生长因子A(VEGA)、糖原合成酶激酶3β(GSK3β)、核因子E2相关因子2(NRF2)和血红素氧合酶1(HO-1)表达的影响。结果CCK8实验结果显示,西黄胶囊和西妥昔单抗对HCT-116细胞活力最佳抑制时间是72 h,IC 50分别为5.28%和170.20 mg/L。与对照组相比,西黄胶囊和西妥昔单抗增加HCT-116细胞的凋亡(P<0.05)、抑制HCT-116细胞迁移以及侵袭(P<0.05)。与单独使用西黄胶囊或西妥昔单抗相比,西黄胶囊联合西妥昔单抗对HCT-116细胞的促凋亡效果和对迁移以及侵袭的抑制效果更加明显(P<0.05)。蛋白质印迹技术结果显示,与对照组比较,西黄胶囊和西妥昔单抗促进HCT-116细胞的BAX表达(P<0.05),抑制BCL2、MMP2、MMP9、ZNF320、VEGA、GSK3B、NRF2、HO-1的表达(P<0.05)。此外,与单独使用西黄胶囊或西妥昔单抗相比,西黄胶囊联合西妥昔单抗的效果更加明显(P<0.05)。结论西黄胶囊联合西妥昔单抗可能通过抑制Nrf2/HO-1信号通路抑制结直肠癌HCT-116细胞的活力、迁移以及侵袭,促进细胞凋亡,且西黄胶囊联合西妥昔单抗的干预效果优于单独使用西黄胶囊或西妥昔单抗。Objective To study the regulatory effect of Xihuang Capsules combined with cetuximab on the apoptosis,migration and invasion of colorectal cancer cells through the Nrf2/HO-1 signaling pathway.Methods Cell counting kit-8(CCK8)was used to determine the effect of Xihuang Capsules and cetuximab on the viability of colon cancer HCT-116 cells.The effects of Xihuang Capsules combined with cetuximab on the apoptosis,migration and invasion of HCT-116 colon cancer cells were detected by flow cytometry,wound healing assay and Transwell assay.Western blot(WB)was used to detect the effects of Xihuang Capsules combined with cetuximab on the expression of colon cancer HCT-116 cell line B Cell lymphoma 2(BCL2),BCL2-associated X protein(BAX),matrix metalloproteinase 2(MMP2),matrix metalloproteinase 9(MMP9),zinc finger protein 232(ZNF320),vascular endothelial growth factor A(VEGA),glycogen synthase kinase 3β(GSK3β),nuclear factor E2-related factor 2(NRF2),and heme oxygenase-1(HO-1).Results CCK8 assay results indicated that the optimal inhibition time of HCT-116 cell viability by Xihuang Capsules and cetuximab was 72 h,with IC 50 values of 5.28%and 170.2 mg/L,respectively.Compared to the control group,Xihuang Capsules and cetuximab significantly increased the apoptosis of HCT-116 cells(P<0.05)and inhibited the migration and invasion of HCT-116 cells(P<0.05).Furthermore,compared to the use of Xihuang Capsules or cetuximab alone,the combination of Xihuang Capsules and cetuximab significantly enhanced the pro-apoptotic effect and inhibition of migration and invasion of HCT-116 cells(P<0.05).WB results showed that,compared to the control group,Xihuang Capsules and cetuximab significantly promoted the expression of BAX(P<0.05)and inhibited the expression of BCL2,MMP2,MMP9,ZNF320,VEGA,GSK3β,NRF2,and HO-1 in HCT-116 cells(P<0.05).Moreover,the effects were more pronounced with the combined use of Xihuang Capsules and cetuximab compared to their individual use(P<0.05).Conclusion Xihuang Capsules and cetuximab may inhibit the viability,mi

关 键 词：西黄胶囊 西妥昔单抗 结直肠癌 Nrf2/HO-1信号通路 

分 类 号：R735[医药卫生—肿瘤]