Effect of NRF1 regulation of the PI3K/AKT pathway on the development of triple-negative breast cancer
[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 mm3vs 15.28±1.29 mm3 vs 16.19±2.17 mm3;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.
NRF1Triple-negative breast cancerPI3KAKTnude miceproliferationLY294002MDA-MB-468
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