摘要
[目的]探究NRF1对三阴性乳腺癌恶性发展的影响及其机制。[方法]将MDA-MB-468细胞随机分为3组:si NC组、si NRF1组以及LY294002组,并转染对应质粒。将MDA-MB-468细胞通过皮下注射至裸鼠体内。根据注射的细胞将小鼠分为:si NC组、si NRF1组以及LY294002组,每组各10只。于注射后第1 w、第2 w和第3 w收集肿瘤体积信息,于第3 w使用戊巴比妥钠(30 mg/kg)剂量处死小鼠。通过TUNEL染色分析肿瘤组织中细胞凋亡率;通过苏木素-伊红染色分析肿瘤组织的病理变化;通过蛋白免疫印迹方法分析肿瘤组织中BAX/Bcl-2以及PI3K/AKT蛋白的表达。[结果]NRF1与si NC组裸鼠比较,si NRF1以及LY294002组裸鼠体内的肿瘤组织的生长速度减慢[(50.36±3.98)mm^(3)vs(15.28±1.29)mm^(3)vs(16.19±2.17)mm^(3);P<0.05]、肿瘤细胞密度降低,肿瘤细胞凋亡率增加[(2.35±0.28)%vs(36.52±6.76)%vs(38.02±8.03)%;P<0.05],促凋亡的BAX蛋白表达增加而抑制凋亡的Bcl-2蛋白表达下降,PI3K与AKT蛋白表达下降(0.69±0.05 vs 0.32±0.03;0.81±0.05 vs 0.21±0.08;P<0.05)。[结论]下调NRF1表达能够抑制裸鼠体内的肿瘤生长,促进肿瘤细胞凋亡。NRF1的这一作用与调控PI3K/AKT通路密切相关。
[Objective]To investigate the effect and mechanism of NRF1 on the malignant development of triple-negative breast cancer(TNBC).[Method]MDA-MB-468 cells were randomly divided into three groups:si NC group,si NRF1 group and LY294002 group,and transfected with corresponding plasmids.MDA-MB-468 cells were subcutaneously injected into nude mice.According to the injected cells,the mice were divided into si NC group,si NRF1 group and LY294002 group,with 10 mice in each group.The tumor volume information was collected at 1,2 and 3 weeks after injection.The mice were sacrificed at the third week after injection with sodium pentobarbital(30mg/kg).The apoptosis rate of tumor tissues was ana-lyzed by TUNEL staining.The pathological changes of tumor tissues were analyzed by HE staining.The expressions of BAX/Bcl-2 and PI3K/AKT proteins in tumor tissues were analyzed by Western Blot.[Result]Compared with the nude mice in the si NC group,the growth rate of tumor tissues in the si NRF1 and LY294002 groups slowed down(50.36±3.98 mm^(3) vs 15.28±1.29 mm^(3) vs 16.19±2.17 mm^(3);P<0.05),the density of tumor cells decreased,the apoptosis rate of tumor cells increased(2.35%±0.28%vs 36.52%±6.76%vs 38.02%±8.03%;P<0.05),the expression of BAX protein that promoted apop-tosis increased,while Bcl-2 protein that inhibited apoptosis decreased,The expression of PI3K and AKT decreased(0.69±0.05 vs 0.32±0.03;0.81±0.05 vs 0.21±0.08;P<0.05).[Conclusions]Down-regulation of NRF1 expression can inhib-it tumor growth rate and promote tumor cell apoptosis in nude mice.Moreover,this effect of NRF1 is closely related to the regu-lation of PI3K/AKT pathway.
作者
李功卓
姜萍
柯龙珠
冷远秀
陈杰
刘杰
王毅强
罗莉
LI Gongzhuo;JIANG Ping;KE Longzhu;LENG Yuanxiu;CHEN Jie;LIU Jie;WANG Yiqiang;LUO Li(Department of Oncology,Guiyang Hospital,Guiyang 550009;Yiyang First Department of Traditional Chinese Medicine Hospital,Yiyang 413000;School of Traditional Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China)
出处
《生物技术》
CAS
2024年第6期749-754,共6页
Biotechnology
基金
贵州省卫生健康委科学技术基金项目(gzwki2021-060)
贵航贵阳医院科研基金国自孵育项目(GHGYYY-KYLX-2022-01)
贵航贵阳医院科研基金项目(GHGYYY-KYLX-2022-02,GHGYYY-KYLX-2022-04)
通用医疗科研基金项目(TYYLKYJJ-2022-028)。
