|Table of Contents|

Experimental study on enhancing the anti-tumor effect of epirubicin by specifically down-regulating the expression of HER-2 in urothelial cancer cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 17
Page:
3206-3212
Research Field:
Publishing date:

Info

Title:
Experimental study on enhancing the anti-tumor effect of epirubicin by specifically down-regulating the expression of HER-2 in urothelial cancer cells
Author(s):
ZHANG Yixiang12LU Tong12WANG Shu12GONG Hua2DAI Qiang2
1.Medical College,Wuhan University of Science and Technology,Hubei Wuhan 430065,China;2.Urology Surgery,the First People's Hospital of Tianmen City,Hubei Tianmen 431700,China.
Keywords:
HER-2epirubicinurinary tract epithelial cancerapoptosis
PACS:
R737.1
DOI:
10.3969/j.issn.1672-4992.2024.17.007
Abstract:
Objective:To observe the effect of specific downregulation of human epidermal growth factor receptor-2(HER-2) expression in urothelial carcinoma cells on the antitumor effect of epirubicin(EPI).Methods:The HER-2 protein expression differences were compared between the normal urothelial cell line SV-HUC-1 and three urothelial carcinoma cell lines T24, SW780, and TCCSUP, and T24 and TCCSUP cells with higher HER-2 expression were screened out.Small interfering RNA(siRNA) targeting HER-2 gene(siHER-2) was designed and introduced into T24 and TCCSUP cells to observe the efficiency of HER-2 downregulation.Subsequently, siHER-2 and EPI were co-introduced into T24 and TCCSUP cells, and the differences in apoptotic levels of cells treated with siHER-2 and EPI alone and in combination were detected using flow cytometry.Western Blot was used to detect the expression levels of PI3K/AKT/mTOR apoptotic pathway-related proteins in each group of cells.Results:HER-2 expression in the three urothelial carcinoma cells was significantly higher than that in the normal urothelial cells(P<0.01).siHER-2 could significantly downregulate HER-2 expression in T24 and TCCSUP cells(P<0.01).The combination of siHER-2 and EPI could significantly increase the apoptotic rate of T24 and TCCSUP cells(P<0.001), while the p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR levels in both cell types were significantly decreased(P<0.001).Conclusion:Specific downregulation of HER-2 expression in urothelial carcinoma cells can effectively enhance the antitumor effect of EPI and may serve as a new strategy for the treatment of urothelial carcinoma.

References:

[1]LOBO N,AFFERI L,MOSCHINI M,et al.Epidemiology,screening,and prevention of bladder cancer[J].Eur Urol Oncol,2022,5(6):628-639.
[2]RICHTERS A,ABEN KKH,KIEMENEY LALM.The global burden of urinary bladder cancer:An update[J].World J Urol,2020,38(8):1895-1904.
[3]BAI XS,YIN HB,KUANG YL,et al.Research advances in antibody-drug conjugates for the treatment of urothelial carcinoma[J].Chongqing Medical University Journal,2023,48(3):346-352.
[4]ZHU S,TANG Y,LI K,et al.Optimal schedule of bacillus calmette-guerin for non-muscle-invasive bladder cancer:A Meta-analysis of comparative studies[J].BMC Cancer,2013,13:332.
[5]MENG L,WANG Z,HOU Z,et al.Study of epirubicin sustained-release chemoablation in tumor suppression and tumor microenvironment remodeling.[J].Front Immunol,2022,20(13):1064047.
[6]郑鹏,程文.膀胱癌靶向治疗的现状[J].医学研究生学报,2019,32(5):552-556. ZHENG P,CHENG W.Current status of targeted therapy for bladder cancer[J].Journal of Medical Postgraduates,2019,32(5):552-556.
[7]VLACHOSTERGIOS PJ,FALTAS BM.Treatment resistance in urothelial carcinoma:An evolutionary perspective[J].Nat Rev Clin Oncol,2018,15(8):495-509.
[8]蒋仕春,贺凯,胡登,等.HER-2、STRT1及PTEN在膀胱尿路上皮细胞癌中的表达及对预后的影响[J].临床误诊误治,2022,35(4):51-54,59. JIANG SC,HE K,HU D,et al.Expression of HER-2,STRT1,and PTEN in urothelial carcinoma of the bladder and their impact on prognosis[J].Clinical Misdiagnosis & Mistreatment,2022,35(4):51-54,59.
[9]KUNTE S,ABRAHAM J,MONTERO AJ.Novel HER-2 targeted therapies for HER-2-positive metastatic breast cancer[J].Cancer,2020,126(19):4278-4288.
[10]中国抗癌协会乳腺癌专业委员会.中国抗癌协会乳腺癌诊治指南与规范(2021年版)[J].中国癌症杂志,2021,31(10):954-1040. Breast Cancer Professional Committee of the Chinese Anti-Cancer Association.Chinese Anti-Cancer Association Guidelines and Standards for the Diagnosis and Treatment of Breast Cancer(2021 Edition)[J].Chinese Journal of Cancer,2021,31(10):954-1040.
[11]MERIC-BERNSTAM F,JOHNSON AM,DUMBRAVA EEI,et al.Advances in HER-2-targeted therapy:Novel agents and opportunities beyond breast and gastric cancer[J].Clin Cancer Res,2019,25(7):2033-2041.
[12]BABJUK M,BOHLE A,BURGER M,et al.EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder:Update 2016[J].Eur Urol,2017,71(3):447-461.
[13]PEI XM,LIU K,XU ZZ,et al.Clinical study of tislelizumab injection combined with gecitabine injection and cisplatin injection in the treatment of advanced urothelial carcinoma[J].Chinese Journal of Clinical Pharmacology,2023,39(11):1533-1537.
[14]李修明,宋殿宾,刘慧,等.血液透析患者合并尿路上皮癌12例临床分析[J].现代肿瘤医学,2021,29(10):1732-1734. LI XM,SONG DB,LIU H,et al.Clinical analysis of 12 patients with urothelial carcinoma complicated by hemodialysis[J].Modern Oncology,2021,29(10):1732-1734.
[15]黄一亮,李超,王继前.经尿道钬激光膀胱肿瘤整块切除术联合化疗治疗肌层浸润性膀胱癌27例[J].中国微创外科杂志,2019,19(11):1036-1038,1056. HUANG YL,LI C,WANG JQ.Transurethral holmium laser en bloc resection combined with chemotherapy for the treatment of 27 cases of muscle-invasive bladder cancer[J].Chinese Journal of Minimally Invasive Surgery,2019,19(11):1036-1038,1056.
[16]DARYANTO B,PURNOMO AF,SEPUTRA KP,et al.Comparison between intravesical chemotherapy epirubicin and mitomycin-C after TURB vs TURB alone with recurrence rate of non-muscle invasive bladder cancer:Meta-analysis[J].Med Arch,2022,76(3):198-201.
[17]李卫胜,李杨东,杨雄,等.表柔比星对比丝裂霉素行膀胱灌注治疗非肌层浸润性膀胱癌的系统评价[J].药物评价研究,2023,46(7):1569-1577. LI WS,LI YD,YANG X,et al.Systematic review of mitomycin C versus epirubicin for intravesical treatment of non-muscle-invasive bladder cancer[J].Drug Evaluation Research,2023,46(7):1569-1577.
[18]吕伟,张淑群,靳耀锋,等.HER-2基因突变在恶性实体瘤中的临床研究进展[J].现代肿瘤医学,2021,29(16):4238-4242. LYU W,ZHANG SQ,JIN YF,et al.Progress in clinical research of HER-2 gene mutation in malignant solid tumors[J].Modern Oncology,2021,29(16):4238-4242.
[19]ALBARAKATI N,AL-SHAREEDA A,RAMADAN M,et al.Interaction between HER-2 and ATM predicts poor survival in bladder cancer patients[J].J Cell Mol Med,2022,26(19):4959-4973.
[20]顾建春,陶双芬,李小平等.联合沉默HER-2和TFF3基因表达抑制胃癌NCI-N87细胞的增殖、迁移和侵袭[J].肿瘤,2018,38(8):750-760. GU JC,TAO SF,LI XP,et al.Inhibition of proliferation,migration,and invasion of gastric cancer NCI-N87 cells by co-silencing HER-2 and TFF3 gene expression[J].Tumor,2018,38(8):750-760.
[21]SHENG X,YAN X,WANG L,et al.Open-label,multicenter,phase Ⅱ study of RC48-ADC,a HER-2-targeting antibody-drug conjugate,in patients with locally advanced or metastatic urothelial carcinoma[J].Clin Cancer Res,2021,27(1):43-51.
[22]GAN K,GAO Y,LIU K,et al.The clinical significance and prognostic value of HER-2 expression in bladder cancer:A Meta-analysis and a bioinformatic analysis[J].Front Oncol,2021,11:653491.
[23]何馨彤,王上,张紫筝,等.HER-2阳性乳腺癌靶向治疗药物的临床研究进展[J].药物评价研究,2021,44(12):2697-2704. HE XT,WANG S,ZHANG ZZ,et al.Clinical research progress of targeted therapies for HER-2-positive breast cancer[J].Drug Evaluation Research,2021,44(12):2697-2704.
[24]OH DY,BANG YJ.HER-2-targeted therapies-a role beyond breast cancer[J].Nat Rev Clin Oncol,2020,17(1):33-48.
[25]BANG YJ,VAN CUTSEM E,FEYEREISLOVA A,et al.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer(ToGA):A phase 3,open-label,randomised controlled trial[J].Lancet,2010,376(9742):687-697.
[26]STRICKLER JH,CERCEK A,SIENA S,et al.Tucatinib plus trastuzumab for chemotherapy-refractory,HER-2 positive,RAS wild-type unresectable or metastatic colorectal cancer(MOUNTAINEER):A multicentre,open-label,phase 2 study[J].Lancet Oncol,2023,24(5):496-508.
[27]KAO CC,CHENG YC,YANG MH,et al.Demethoxycurcumin induces apoptosis in HER-2 overexpressing bladder cancer cells through degradation of HER-2 and inhibiting the PI3K/Akt pathway[J].Environ Toxicol,2021,36(11):2186-2195.
[28]LI X,WU C,CHEN N,et al.PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma[J].Oncotarget,2016,7(22):33440-33450.
[29]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 YL,et al.Research progress of PI3K/AKT/mTOR pathway inhibitors in bladder cancer[J].Modern Oncology,2023,31(3):575-579.
[30]段兰英,白俊.PI3K/AKT/mTOR信号传导通路在膀胱癌中作用的研究进展[J].中国临床研究,2021,34(11):1569-1573. DUAN LY,BAI J.Research progress on the role of the PI3K/AKT/mTOR signaling pathway in bladder cancer[J].Chinese Clinical Research,2021,34(11):1569-1573.

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Last Update: 2024-07-31