下调SCD1表达增敏RSL3诱导铁死亡抑制膀胱癌细胞生长

邓俊, 刘文

湖南师范大学学报医学版 ›› 2023, Vol. 20 ›› Issue (6) : 49-54.

PDF(8334 KB)
PDF(8334 KB)
湖南师范大学学报医学版 ›› 2023, Vol. 20 ›› Issue (6) : 49-54.
基础医学

下调SCD1表达增敏RSL3诱导铁死亡抑制膀胱癌细胞生长

  • 邓俊, 刘文
作者信息 +

Down-regulating SCD1 expression sensitizes RSL3 induced ferroptosis and inhibited bladder cancer cell growth

  • DENG Jun, LIU Wen
Author information +
文章历史 +

摘要

目的:探究SCD1蛋白表达对铁死亡激活剂RSL3诱导膀胱癌细胞铁死亡能力的作用及机制。方法:SCD1小干扰RNA(siRNA)、特异性SCD1抑制剂 (A9)处理或联合RSL3处理T24细胞;CCK-8、克隆集落形成实验检测抑制SCD1表达或联合RSL3对细胞增殖及克隆集落形成能力的影响;丙二醛(MDA)及脂质过氧化物(LPO)含量测定分析下调SCD1对RSL3诱导膀胱癌细胞T24铁死亡能力的影响;最后通过蛋白质印迹检测谷胱甘肽过氧化酶4(GPX4)表达。结果:siRNA沉默及A9处理均降低膀胱癌细胞T24增殖及克隆集落形成能力;相对单用组,两种抑制SCD1方法联合RSL3进一步增加膀胱癌细胞MDA及LPO含量,并且增加对增殖及克隆集落形成的抑制程度。此外,抑制SCD1增强RSL3对GPX4蛋白表达的抑制作用。结论:下调SCD1通过增强RSL3对GPX4蛋白表达的抑制,诱发铁死亡发挥抑制膀胱癌细胞生长的作用。

Abstract

Objective To explore the effect and mechanism of SCD1 protein expression on the ability of ferroptosis activator RSL3 to induce ferroptosis in bladder cancer cells. Method T24 cells were treated with SCD1 small interfering RNA (siRNA), specific SCD1 inhibitor (A9) or combined with RSL3; The effects of inhibiting SCD1 expression or combining with RSL3 on cell proliferation and clonogenesis were detected by CCK-8 and clonogenesis assay; Malondialdehyde (MDA) and lipid peroxides (LPO) were determined to investigate the effect of down-regulated SCD1 on the ability of RSL3 to induce ferroptosis in bladder cancer cells T24; Finally, glutathione peroxidase 4(GPX4) expression was detected by western blot. Results Both siRNA silencing and A9 treatment decreased the proliferation and colony formation ability of bladder cancer cells. Compared with the single treatment group, The two SCD1 inhibition methods combined with RSL3 further increased the MDA and LPO content in the cells, and enhanced the degree of inhibition on the proliferation and clonal colony formation of bladder cancer cells. In addition, inhibition of SCD1 enhanced the inhibitory effect of RSL3 on GPX4 protein expression. Conclusion Down-regulation of SCD1 can inhibit the growth of bladder cancer cells by enhancing the inhibition of GPX4 protein expression by RSL3 and inducing ferroptosis.

关键词

膀胱癌 / 铁死亡 / SCD1 / GPX4

Key words

bladder cancer / ferroptosis / SCD1 / GPX4

引用本文

导出引用
邓俊, 刘文. 下调SCD1表达增敏RSL3诱导铁死亡抑制膀胱癌细胞生长[J]. 湖南师范大学学报医学版. 2023, 20(6): 49-54
DENG Jun, LIU Wen. Down-regulating SCD1 expression sensitizes RSL3 induced ferroptosis and inhibited bladder cancer cell growth[J]. Journal of Hunan Normal University(Medical Science). 2023, 20(6): 49-54
中图分类号: R737.14   

参考文献

[1] VAN HOOGSTRATEN LMC, VRIELING A, VAN DER HEIJDEN AG, et al. Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice[J]. Nat Rev Clin Oncol, 2023, 20: 287-304.
[2] PENG M, XIAO D, BU Y, et al.Novel Combination Therapies for the Treatment of Bladder Cancer[J]. Front Oncol, 2020, 10: 539527.
[3] SZABADOS B, KOCKX M, ASSAF ZJ, et al.Final Results of Neoadjuvant Atezolizumab in Cisplatin-ineligible Patients with Muscle-invasive Urothelial Cancer of the Bladder[J]. Eur Urol, 2022, 82: 212-222.
[4] SIEFKER-RADTKE AO, NECCHI A, PARK SH, et al.Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study[J]. Lancet Oncol, 2022, 23: 248-258.
[5] KANG N, SON S, MIN S, et al.Stimuli-responsive ferroptosis for cancer therapy[J]. Chem Soc Rev, 2023, 52: 3955-3972.
[6] REN Y, MAO X, XU H, et al.Ferroptosis and EMT: key targets for combating cancer progression and therapy resistance[J]. Cell Mol Life Sci, 2023, 80: 263.
[7] SEN U, COLEMAN C, SEN T.Stearoyl coenzyme A desaturase-1: multitasker in cancer, metabolism, and ferroptosis[J]. Trends Cancer, 2023, 9: 480-489.
[8] MIN JY, KIM DH.Stearoyl-CoA Desaturase 1 as a Therapeutic Biomarker: Focusing on Cancer Stem Cells[J]. Int J Mol Sci, 2023, 2424(10) : 8951.
[9] WU T, WAN J, QU X, et al.Nodal promotes colorectal cancer survival and metastasis through regulating SCD1-mediated ferroptosis resistance[J]. Cell Death Dis, 2023, 14: 229.
[10] PRESLER M, WOJTCZYK-MIASKOWSKA A, SCHLICHTHOLZ B, et al.Increased expression of the gene encoding stearoyl-CoA desaturase 1 in human bladder cancer[J]. Mol Cell Biochem, 2018, 447: 217-224.
[11] CHEN Z, WANG W, ABDUL RAZAK SR, et al.Ferroptosis as a potential target for cancer therapy[J]. Cell Death Dis, 2023, 14: 460.
[12] ZHU X, LI S. Ferroptosis, Necroptosis,Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance[J]. Adv Sci (Weinh) , 2023, 10: e2300824.
[13] DENG J, PENG M, WANG Z, et al.Novel application of metformin combined with targeted drugs on anticancer treatment[J]. Cancer Sci, 2019, 110: 23-30.
[14] CHEN L, HAN X.Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future[J]. J Clin Invest, 2015, 125: 3384-3391.
[15] LINGEL H, BRUNNER-WEINZIERL MC.CTLA-4 (CD152) : A versatile receptor for immune-based therapy[J]. Semin Immunol, 2019, 42: 101298.
[16] PIAO C, CUI X, ZHAN B, et al.Inhibition of stearoyl CoA desaturase-1 activity suppresses tumour progression and improves prognosis in human bladder cancer[J]. J Cell Mol Med, 2019, 23: 2064-2076.
[17] ALJOHANI AM, SYED DN, NTAMBI JM.Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism[J]. Trends Endocrinol Metab, 2017, 28: 831-842.
[18] CHEN H, QI Q, WU N, et al.Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutatnt colorectal cancer[J]. Redox Biol, 2022, 55: 102426.
[19] MA MKF, LAU EYT, LEUNG DHW, et al.Stearoyl-CoA desaturase regulates sorafenib resistance via modulation of ER stress-induced differentiation[J]. J Hepatol, 2017, 67: 979-990.
[20] LIU Y, LIU X, WANG H, et al.Agrimonolide inhibits cancer progression and induces ferroptosis and apoptosis by targeting SCD1 in ovarian cancer cells[J]. Phytomedicine, 2022, 101: 154102.
[21] XUAN Y, WANG H, YUNG MM, et al.SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells[J]. Theranostics, 2022, 12: 3534-3552.
[22] LI Z, ZHU Z, LIU Y, et al.Function and regulation of GPX4 in the development and progression of fibrotic disease[J]. J Cell Physiol, 2022, 237: 2808-2824.
[23] CHANG MT, TSAI LC, NAKAGAWA-GOTO K, et al.Phyto-sesquiterpene lactones DET and DETD-35 induce ferroptosis in vemurafenib sensitive and resistant melanoma via GPX4 inhibition and metabolic reprogramming[J]. Pharmacol Res, 2022, 178: 106148.

基金

湖南省自然科学基金项目“下调Clusterin通过抑制SCD1诱导铁死亡增敏吡柔比星抑制膀胱癌生长的作用机制研究”(2023JJ40372); 长沙市自然科学基金“Clusterin介导外泌体促进膀胱癌生长转移及在吡柔比星治疗耐受中的作用及机制研究”(kq2208125)

PDF(8334 KB)

Accesses

Citation

Detail

段落导航
相关文章

/