|Table of Contents|

Reversal of cisplatin resistance in human triple-negative breast cancer MDA-MB-231 cells by using tubeimoside-1 and its mechanism

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

Issue:
2024 17
Page:
3172-3180
Research Field:
Publishing date:

Info

Title:
Reversal of cisplatin resistance in human triple-negative breast cancer MDA-MB-231 cells by using tubeimoside-1 and its mechanism
Author(s):
JIANG Haopeng1; TANG Donghao1; CAI Jialuo1; WEI Yufang2; YUAN Yi1
1.Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China;2.Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China．
Keywords:
triple-negative breast cancer; tubeimoside-1; cisplatin; Wnt/β-catenin; drug resistance
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2024.17.003
Abstract:
Objective:To investigate the reversal effect of tubeimoside-1(TBMS-1) on cisplatin(DDP) resistance in triple-negative breast cancer and its possible mechanism.Methods:A cisplatin-resistant triple-negative breast cancer cell line MDA-MB-231/DDP was constructed,and the resistance index（RI) of the cells was detected by CCK-8 method to evaluate the inhibitory effect of TBMS-1 and the reversal effect on DDP-resistant strains.The control group,DDP group,TBMS-1 group and TBMS-1+DDP group of MDA-MB-231/DDP were set up in the experiment.The proliferation ability of each group was detected by plate cloning experiment.The ROS level of each cell was detected by DCFH-DA reactive oxygen fluorescent probe.TUNEL staining and flow cytometry were used to detect the apoptosis of each group.The expression levels of β-catenin total protein and nuclear protein,as well as Wnt3a,Bcl-2 and Bax were detected by Western blot.MDA-MB-231/DDP cells were divided into control group,DDP group,Adavivint group（Wnt/β-catenin pathway inhibitor) and DDP+Adavivint group.The total protein and nuclear protein of β-catenin,and the expression levels of Wnt3a,Bcl-2 and Bax were detected by Western blot.Results:TBMS-1 inhibited the proliferation of MDA-MB-231/DDP cells in a concentration-dependent manner,reduced the IC50 value of DDP to MDA-MB-231/DDP cells,and reversed its drug resistance（P<0.05).TBMS-1 can enhance the effect of DDP-induced apoptosis and ROS accumulation in MDA-MB-231/DDP cells,and inhibit the abnormal activation of Wnt/β-catenin.Conclusion:TBMS-1 has a good reversal effect on cisplatin resistance in MDA-MB-231/DDP cells,which may be achieved by inhibiting the activation of Wnt/β-catenin signaling pathway.

References:

［1］XIA C,DONG X,LI H,et al.Cancer statistics in China and United States,2022:Profiles,trends,and determinants［J］.Chin Med J（Engl)，2022，135(5):584-590.
［2］DERAKHSHAN F,REIS-FILHO JS.Pathogenesis of triple-negative breast cancer［J］.Annu Rev Pathol,2022,17:181-204.
［3］LUGONES Y,LOREN P,SALAZAR LA.Cisplatin resistance:Genetic and epigenetic factors involved［J］.Biomolecules,2022,12(10):1365.
［4］FU R,ZHAO B,CHEN M,et al.Moving beyond cisplatin resistance:Mechanisms,challenges,and prospects for overcoming recurrence in clinical cancer therapy［J］.Med Oncol,2023,41(1):9.
［5］WANG CL,GAO MZ,GAO DM,et al.Tubeimoside-1:A review of its antitumor effects,pharmacokinetics,toxicity,and targeting preparations［J］.Front Pharmacol,2022,13:941270.
［6］SHI H,BI H,SUN X,et al.Tubeimoside-1 inhibits the proliferation and metastasis by promoting miR-126-5p expression in non-small cell lung cancer cells［J］.Oncol Lett,2018,16(3):3126-3134.
［7］GHANDADI M,VALADAN R,MOHAMMADI H,et al.Wnt-β-catenin signaling pathway,the Achilles' heels of cancer multidrug resistance［J］.Curr Pharm Des,2019,25(39):4192-4207.
［8］盛佳钰,时百玲,陈红风.三阴性乳腺癌MDA-MB-231顺铂耐药细胞株的建立及鉴定［J］.肿瘤防治研究,2016,43（3):175-180. SHENG JY,SHI BL,CHEN HF.Establishment and appraisal of DDP resistant variant of triple negative breast cancer cell line MDA-MB-231［J］.Cancer Res Prev Treat,2016,43（3):175-180.
［9］KASHYAP D,PAL D,SHARMA R,et al.Global increase in breast cancer incidence:Risk factors and preventive measures［J］.Biomed Res Int,2022,2022:9605439.
［10］RAJPUT S,SHARMA PK,MALVIYA R.Biomarkers and treatment strategies for breast cancer recurrence［J］.Curr Drug Targets,2023,24(15):1209-1220.
［11］MAKOVEC T.Cisplatin and beyond:Molecular mechanisms of action and drug resistance development in cancer chemotherapy［J］.Radiol Oncol,2019,53(2):148-158.
［12］TSVETKOVA D,IVANOVA S.Application of approved cisplatin derivatives in combination therapy against different cancer diseases［J］.Molecules,2022,27(8):2466.
［13］KIM Y,BAE YJ,KIM JH,et al.Wnt/β-catenin pathway is a key signaling pathway to trastuzumab resistance in gastric cancer cells［J］.BMC Cancer,2023,23(1):922.
［14］MOHANTY A,NAM A,SRIVASTAVA S,et al.Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer［J］.Sci Adv,2023,9(41):eade3816.
［15］CHI C,HOU W,ZHANG Y,et al.PDHB-AS suppresses cervical cancer progression and cisplatin resistance via inhibition on Wnt/β-catenin pathway［J］.Cell Death Dis,2023,14(2):90.
［16］蔡家洛,朱锐秋,李森,等.炎症癌相关成纤维细胞介导结直肠癌细胞耐药的机制研究［J］.中国癌症杂志,2023,33(12):1065-1072. CAI JL,ZHU RQ,LI S,et al.Mechanism of inflammatory cancer-associated fibroblast-mediated drug resistance in colorectal cancer cells［J］.China Oncology,2023,33(12):1065-1072.
［17］陈影,庄蕾,张丹红,等.低氧微环境通过TGFBI调控Wnt/β-catenin通路介导胰腺癌化疗耐药及机制研究［J］.现代肿瘤医学,2024,32（1):42-46. CHEN Y,ZHUANG L,ZHANG DH,et al.The role and mechanism of hypoxia on drug resisitance of pancreatic cancer through TGFBI mediated activation of Wnt/β-catenin signaling pathway［J］.Modern Oncology,2024,32（1):42-46.
［18］LI L,LIU HC,WANG C,et al.Overexpression of β-Catenin induces cisplatin resistance in oral squamous cell carcinoma［J］.Biomed Res Int,2016,2016:5378567.
［19］ZHU X,FENG J,FU W,et al.Effects of cisplatin on the proliferation,invasion and apoptosis of breast cancer cells following β-catenin silencing［J］.Int J Mol Med,2020,45(6):1838-1850.
［20］戴金芳,赵益,孙有智.乳腺癌中医病因病机探析［J］.光明中医,2017,32（7):1069-1072. DAI JF,ZHAO Y,SUN YZ.Analysis of TCM etiology and pathogenesis of breast cancer［J］.Guangming Journal of Chinese Medicine,2017,32（7):1069-1072.
［21］李菡,武康雄,史阔豪,等.土贝母化学成分、药理作用及临床应用研究进展［J］.中国中药杂志,2021,46(17):4314-4322. LI H,WU KX,SHI KH,et al.Research progress on chemical constituents,pharmacological activitiesand clinical application of Bolbostemma paniculatum［J］.China Journal of Chinese Materia Medica,2021,46(17):4314-4322.
［22］国家药典委员会.中华人民共和国药典:一部［M］.北京:中国医药科技出版社,2020:17-18. Chinese Pharmacopoeia Commission.Chinese Pharmacopoeia:I department［M］.Beijing:Press of Chemistry,2020:17-18.
［23］HAO W,WANG S,ZHOU Z.Tubeimoside-1（TBMS1) inhibits lung cancer cell growth and induces cells apoptosis through activation of MAPK-JNK pathway［J］.Int J Clin Exp Pathol,2015,8(10):12075-12083.
［24］JIANG SL,GUAN YD,CHEN XS,et al.Tubeimoside-1,a triterpenoid saponin,induces cytoprotective autophagy in human breast cancer cells in vitro via Akt-mediated pathway［J］.Acta Pharmacol Sin,2019,40(7):919-928.
［25］YANG JB,KHAN M,HE YY,et al.Tubeimoside-1 induces oxidative stress-mediated apoptosis and G0/G1 phase arrest in human prostate carcinoma cells in vitro［J］.Acta Pharmacol Sin,2016,37(7):950-962.
［26］BIAN Q,LIU P,GU J,et al.Tubeimoside-1 inhibits the growth and invasion of colorectal cancer cells through the Wnt/β-catenin signaling pathway［J］.Int J Clin Exp Pathol,2015,8(10):12517-12524.

Memo

Memo:
National Natural Science Foundation of China(No.81973625);国家自然科学基金资助项目（编号：81973625）;上海市普陀区卫生系统科技创新项目（编号：ptkwws202204）;上海中医药大学预算内项目（编号：2021LK052）
Last Update: 2024-07-31