基于核因子相关因子2/血红素加氧酶-1信号通路探讨异荭草素对乳腺癌细胞恶性生物学行为的影响  

Effect of Isoorientin on Malignant Biological Behavior of Breast Cancer Cells Based on Nuclear Factor-related Factor 2/heme Oxygenase-1 Signaling Pathway

作　　者：王喻 庞兴华 田一鸣 路灿[4] 苑著[5] WANG Yu;PANG Xing-hua;TIAN Yi-ming;LU Can;YUAN Zhu(Department of Breast Surgery,Bejing Hepingli Hospital,Beijing,100013,China;Second Department of Surgery,Beijing Fengtai Hospital of Integrated Traditional Chinese and Western Medicine,Beijing,100072,China;Department of Surgery,Huairou Maternal and Child Health Care Hospital,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing,101400,China;Department of Breast Surgery,Women's Health Centre,Daxing District Maternal and Child Health Care Hospital of Bejing,Beijing,102600,China;Department of General Surgery,Beijing Friendship Hospital,Capital Medical University,Beijing,100050,China)

机构地区：[1]北京市和平里医院乳腺外科,北京100013 [2]北京市丰台中西医结合医院外二科,北京100072 [3]首都医科大学附属北京妇产医院怀柔妇幼保健院外科,北京101400 [4]北京市大兴区妇幼保健院乳腺外科,北京102600 [5]首都医科大学附属北京友谊医院普外科,北京100050

出　　处：《现代生物医学进展》2023年第16期3021-3026,共6页Progress in Modern Biomedicine

基　　金：北京市属医院科研培育计划项目(PX20190102)。

摘　　要：目的:探讨异荭草素(ISO)对乳腺癌(BC)细胞恶性生物学行为及核因子相关因子2(Nrf2)/血红素加氧酶-1(HO-1)信号通路的影响。方法:体外培养人BC细胞系MDA-MB-231并分组:MDA-MB-231组、MDA-MB-231+ISO组(100μmol/L ISO处理)、MDA-MB-231+ISO+OE-NC组(转染OE-NC后用100μmol/L ISO处理)、MDA-MB-231+ISO+OE-Nrf2组(转染OE-Nrf2后用100μmol/L ISO处理)。采用细胞计数试剂盒-8(CCK-8)检测MDA-MB-231细胞增殖;流式细胞术检测MDA-MB-231细胞周期和凋亡;Transwell实验检测MDA-MB-231细胞的侵袭和迁移能力;Western blot检测Nrf2/HO-1信号通路相关蛋白及凋亡蛋白表达。结果:与MDA-MB-231组相比,MDA-MB-231+ISO组、MDA-MB-231+ISO+OE-NC组细胞活力、S期和G2期细胞比例、迁移和侵袭能力、B淋巴细胞瘤-2(Bcl-2)、Nrf2、HO-1、基质金属蛋白酶-9(MMP-9)蛋白水平显著下降(P<0.05),细胞凋亡率、G1/G0期细胞比例以及Bax、cleaved-Caspase-3蛋白水平显著上升(P<0.05)。与MDA-MB-231+ISO组相比,MDA-MB-231+ISO+OE-Nrf2组细胞活力、S期和G2期细胞比例、迁移和侵袭能力、Bcl-2、Nrf2、HO-1、MMP-9蛋白水平显著上升(P<0.05),细胞凋亡率、G1/G0期细胞比例以及Bax、cleaved-Caspase-3蛋白水平显著降低(P<0.05)。结论:ISO可能通过抑制Nrf2/HO-1信号通路,抑制MDA-MB-231细胞恶性增殖、迁移和侵袭等行为。Objective: To investigate the influences of isoorientin(ISO) on malignant biological ehavior of breast cancer(BC) cells and nuclear factor-related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway. Methods: Human BC cell line MDA-MB-231 was cultured in vitro and separated into groups: MDA-MB-231 group, MDA-MB-231+ISO group(100 μmol/L ISO treatment),MDA-MB-231+ ISO+OE-NC group(treated with 100 μmol/L ISO after transfection of OE-NC), and MDA-MB-231+ISO+OE-Nrf2group(treated with 100 μmol/L ISO after transfection of OE-Nrf2). MDA-MB-231 cells proliferation was detected by cell count kit-8(CCK-8). Flow cytometry was used to detect MDA-MB-231 cells cycle and apoptosis. Transwell assay was used to detect the invasion and migration abilities of MDA-MB-231 cells. Western blot was used to detect the expression of Nrf2/HO-1 signaling pathway-related proteins and apoptosis proteins. Results: Compared with MDA-MB-231 group, MDA-MB-231+ISO group and MDA-MB-231+ISO+OE-NC group had obviously lower cell viability, S phase and G2 phase cells ratios, migration and invasion abilities, B-lymphocytoma-2(Bcl-2), Nrf2, HO-1, matrix metalloproteinase-9(MMP-9) protein levels(P<0.05), and obviously higher apoptosis rate, G1/G0phase cells ratios, and Bax and cleaved-Caspase-3 protein levels(P<0.05). Compared with MDA-MB-231+ISO group, MDAMB-231+ISO+OE-Nrf2 group had obviously higher cell viability, S phase and G2 phase cells ratios, migration and invasion abilities,Bcl-2, Nrf2, HO-1, MMP-9 protein levels(P<0.05), and obviously lower apoptosis rate, G1/G0 phase cells ratios, and Bax and cleaved-Caspase-3 protein levels(P<0.05). Conclusion: ISO may inhibit the malignant proliferation, migration and invasion of MDA-MB-231 cells by inhibiting the Nrf2/HO-1 signaling pathway.

关 键 词：异荭草素 核因子相关因子2/血红素加氧酶-1通路 增殖 迁移 侵袭 乳腺癌 

分 类 号：R-33[医药卫生] R737.9