Inhibitory Effect of Hyperoside on Prodiferation of Bladder Urothelial Carcinoma Cells via NOX4

doi:10.3870/j.issn.1672-8009.2026.01.006

Abstract

Abstract: Objective To analyze the inhibitory effect of hyperoside on inhibiting the proliferation of bladder urothelial carcinoma(BLCA)cells and the mechanism. Methods Cell proliferation was detected by CCK-8 and colony formation assays.The expression level of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in cells under different concentration of hyperoside and intervention time,and the expression levels of mTOR,AKT,S6 cells and NOX4 proteins were detected by Western blotting. Results The proliferation ability of cells,number of cell colonies,volume and mass of transplanted tumor tissues,and expression level of Ki67 protein were significantly decreased in the hyperoside group(P<0.05).The expression level of NOX4 was significantly decreased with the increase of the treatment time and concentration of hyperoside(P<0.05).Compared with those in the control group,the expression levels of p-mTOR,p-S6,p-Akt and NOX4,and number of colonies were significantly decreased in the hyperoside group,while the above indexes were significantly increased in the NOX4 overexpression group and the hyperoside +NOX4overexpression group(P<0.05). Conclusion Hyperoside can inhibit BLCA proliferation by supressing the expression of NOX4.

Key words: hyperoside, bladder urothelial carcinoma, NOX4 protein

CLC Number:

GAO Huilin, WANG Hailin, Meng Qi. Inhibitory Effect of Hyperoside on Prodiferation of Bladder Urothelial Carcinoma Cells via NOX4[J]. Journal of Medical Molecular Biology, 2026, 23(1): 43-50.

References

[1] 鲁奕君,陈鸿凯,蔡亮,等.lncRNA RP11-635 L1.2在膀胱癌组织中的表达及对膀胱癌细胞增殖和侵袭的影响[J].临床误诊误治,2022,35(11):102-107.
LU Y J,CHEN H K,CAI L,et al.Expression of lncRNA RP11-635 L1.2 in bladder cancer tissue and its effect on the proliferation and invasion of bladder cancer cells[J].Clin Misdiagn Misther,2022,35(11):102-107.
[2] 王丽丽,崔艳歆,崔华硕.外周血MIR-143、miR-33a水平与膀胱癌临床病理特征及化疗疗效的关系[J].分子诊断与治疗杂志,2022,14(6):966-969,974.
WANG L L,CUI Y X,CUI H S.Relationship between peripheral miR-143 and mir-33a levels and clinicopathological char-acteristics of bladder cancer and the efficacy of chemotherapy[J].Mol Diagn Ther,2022,14(6):966-969,974.
[3] POWLES T,PARK S H,CASERTA C,et al.Avelumab first-line maintenance for advanced urothelial carcinoma:Results from the JAVELIN bladder 100 trial after ≥2 years of follow-up[J].J Clin Oncol,2023,41(19):3486-3492.
[4] QIU J,ZHANG T,ZHU X,et al.Hyperoside induces br-east cancer cells apoptosis via ROS-mediated NF-κB signaling pathway[J].Int J Mol Sci,2019,21(1):131.
[5] MU Z,SHEN S,TANG L,et al.Hyperin promotes proliferation,migration,and invasion of HTR-8/SVneo trophoblast cells via activation of JAK1/STAT3 pathway in recurrent spontaneous abortions[J].Heliyon,2023,9(1):e12958.
[6] LIU B,TU Y,HE W,et al.Hyperoside attenuates renal aging and injury induced by D-galactose via inhibiting AMPK-ULK1 signaling-mediated autophagy[J].Aging,2018,10(12):4197-4212.
[7] 鄂璐莎,田志强,王婷.金丝桃苷通过TLR4/NF-κB信号通路对动脉粥样硬化小鼠的干预作用[J].广西医学,2023,45(3):302-308.
E L S,TIAN Z Q,WANG T.Intervention effect of hyperoside via TLR4/NF-κB signaling pathway on mice with atherosclerosis[J].Guangxi Med J,2023,45(3):302-308.
[8] 高鑫,张淑芳.膀胱癌关键基因的筛选及预后相关性分析[J].感染、炎症、修复,2022,23(3):131-137.
GAO X,ZHANG S F.Screening of key genes and correlation analysis of prognosis in bladder cancer[J].Infection,Inflammation,Repair,2022,23(3):131-137.
[9] VANTAKU V,PUTLURI V,BADER D A,et al.Epigenetic loss of AOX1 expression via EZH2 leads to metabolic deregulations and promotes bladder cancer progression[J].Oncogene,2020,39(40):6265-6285.
[10] 杨为潇,邵彦翔,胡旭,等.卡介苗对比表柔比星膀胱内灌注治疗非肌层浸润性膀胱癌的随机对照研究[J].四川大学学报(医学版),2021,52(2):326-333.
YANG W X,SHAO Y X,HU X,et al.A Randomized controlled study of intravesical instillation therapy of bacillus valmette-guérin vs.rpirubicinin treating non-muscular invasive bladder cancer[J].J.Sichuan Univ(Med Sci Ed),2021,52(2):326-333.
[11] 闫文佳,卞伟,肖虹.NOX4在恶性肿瘤中的研究进展[J].生命的化学,2024,44(5):910-917.
YAN W J,BIAN W,XIAO H.Research progress of NOX4 in malignant tumors[J].Chem Life,2024,44(5):910-917.
[12] 陆珏,蔡梦娇,张莹冰.血清NOX4 MUC1表达水平与Ⅲ期非小细胞肺癌患者放疗疗效及随访1年总生存率的关系研究[J].河北医学,2024,30(12):2028-2033.
LU Y,CAI M J,ZHANG Y B.Relationship between expression levels of serum NOX4 and MUC1 with radiotherapy efficacy and 1-year overall survival rate in patients with stage Ⅲ non-small cell lung cancer[J].Hebei Med,2024,30(12):2028-2033.
[13] 郭丽,韩晨阳.还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶4(NOX4)在肝癌细胞诱导巨噬细胞M2型极化中的作用[J].中华微生物学和免疫学杂志,2020,40(12):934-940.
GUO L,HAN C Y.Role of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)in hepatoma cell-induced M2 polarization of macrophages[J].Chin J Microbiol Immunol,2020,40(12):934-940.
[14] 赵建壹,陈萌萌,刘晓,等.NOX4在胃癌评价中的意义探索[J].中国现代普通外科进展,2024,27(1):36-41.
ZHAO J Y,CHEN M M,LIU X,et al.Exploration of the significance of NOX4 in the evaluation of gastric cancer[J].Chin J Curr Adv Gen Surg,2024,27(1):36-41.
[15] 陈康,邢基,张云龙,等.PI3K/AKT/mTOR通路抑制剂在膀胱癌中的研究进展[J].现代肿瘤医学,2023,31(3):575-579.
CHEN K,XING J,ZHANG Y L,et al.Research progress of PI3K/AKT/mTOR pathway inhibitors in bladder cancer[J].J Mod Oncol,2023,31(3):575-579.
[16] LIU J,VELU P,VIJAYALAKSHMI A,et al.Betanin inhibits PI3K/AKT/mTOR/S6 signaling pathway,cell growth and death in osteosarcoma MG-63 cells[J].Environ Toxicol,2023,38(9):2173-2181.
[17] HUANG M,QIN B,XIE Z,et al.RCN3 functions as a tumor promoter in colorectal cancer by modulating the GRP78-PI3K-AKT signaling pathway[J].Oncogene,2025,44(40):3850-3863.
[18] 吴秀东,韦堂墙,于晓倩.布托啡诺调节PI3K/AKT/mTOR信号通路对膀胱癌细胞恶性生物学行为的影响[J].现代肿瘤医学,2024,32(5):805-810.
WU X D,WEI T Q,YU X Q.Effect of butorphanol on malignant biological behavior of bladder cancer cells by regulating PI3K/AKT/mTOR signaling pathway[J].J Mod Oncol,2024,32(5):805-810.