|Table of Contents|

The role and mechanism of hypoxia on drug resistance of pancreatic cancer through TGFBI mediated activation of Wnt/β-catenin signaling pathway

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

Issue:
2024 01
Page:
42-46
Research Field:
Publishing date:

Info

Title:
The role and mechanism of hypoxia on drug resistance of pancreatic cancer through TGFBI mediated activation of Wnt/β-catenin signaling pathway
Author(s):
CHEN Ying1; ZHUANG Lei1; 2; ZHANG Danhong1; SHENG Liming1; SUI Yang3
1.Zhejiang Cancer Hospital,Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Zhejiang Hangzhou 310022,China;2.the Second Clinical Medical College,Zhejiang Chinese Medical University,Zhejiang Hangzhou 310053,China;3.Department of Laboratory Medicine,Suzhou Municipal Hospital,the Affiliated Suzhou Hospital of Nanjing Medical University,Jiangsu Suzhou 215008,China.
Keywords:
tumor microenvironment; Wnt/β-catenin signaling pathway; epithelial-mesenchymal transition(EMT); TGFBI
PACS:
R735.9
DOI:
10.3969/j.issn.1672-4992.2024.01.007
Abstract:
Objective:To study the role and the mechanism of hypoxia on drug resistance of pancreatic cancer through TGFBI.Methods:Cell survival was detected by CCK-8 assay.Western blotting technology was used to detect the expression levels of target proteins.ImageJ was used analyze the gray value of protein bands.The level of TGFBI in Panc-1 cells was downregulated by RNAi technology.Results:The expression of TGFBI in Panc-1 was significantly higher than that in normal cells.Hypoxia contributed to cell proliferation of Panc-1 cells and relieved the inhibition of cisplatin on Panc-1 cells.But hyperoxia exhibited reverse effects on Panc-1 cells.Hypoxia promoted the expression of TGFBI and forwarded the EMT behavior.Hypoxia regulated cell proliferation and the inhibition of cisplatin through TGFBI gene.Hypoxia increased the activation of Wnt/β-catenin signaling pathway through TGFBI followed by EMT behavior.Conclusion:Hyperoxia promoted cell proliferation and drug resistance of pancreatic cancer through regulation of TGFBI.Hypoxia contributed to activation of Wnt/β-catenin signaling pathway and promoted EMT behavior through TGFBI.

References:

[1]KLEIN AP.Pancreatic cancer epidemiology:understanding the role of lifestyle and inherited risk factors［J］.Gastroenterol Hepatol,2021,18(7):493-502.
[2] ZHAO ZY,LIU W.Pancreatic cancer:A review of risk factors,diagnosis,and treatment［J］.Technol Cancer Res Treat,2020,19(10):1-13.
[3] NUSSINOV R,TSAI CJ,JANG H,et al.Anticancer drug resistance:An update and perspective［J］.Drug Resist Updat,2021,59(10):796-796.
[4] GANESAN S,MATHEWS V,VYAS N,et al.Microenvironment and drug resistance in acute myeloid leukemia:Do we know enough［J］.Int J Cancer,2022,150(9):1401-1411.
[5] LECKER LSM,BERLATO C,MANIATI E,et al.TGFBI production by macrophages contributes to an immunosuppressive microenvironment in ovarian cancer［J］.Cancer Res,2021,81(22):5706-5719.
[6] CORONA A,BLOBE GC.The role of the extracellular matrix protein TGFBI in cancer［J］.Cell Signal,2021,84(8):28-29.
[7] YANG LM,CUI RL,LI YG,et al.Hypoxia-induced TGFBI as a serum biomarker for laboratory diagnosis and prognosis in patients with pancreatic ductal adenocarcinoma［J］.Lab Med,2020,51(4):352-361.
[8] COSTANZA B,RADEMAKER G,TIAMIOU A,et al.Transforming growth factor beta-induced,an extracellular matrix interacting protein,enhances glycolysis and promotes pancreatic cancer cell migration［J］.Int J Cancer,2019,145(6):1570-1584.
[9] CONCONI MT,BAIBUERA S,GUIDOLIN D,et al.Effects of hyperbaric oxygen on proliferative and apoptotic activities and reactive oxygen species generation in mouse fibroblast 3T3/J2 cell line［J］.J Investig Med,2003,51(4):227-232.
[10] GOMEZ CR,KNUTSON GJ,CLIFTON KB,et al.Age-dependent response of murine female bone marrow cells to hyperbaric oxygen［J］.Biogerontology,2012,13(3):287-297.
[11] XIAO Y,YU DH.Tumor microenvironment as a therapeutic target in cancer［J］.Pharmacol Ther,2021,221(1):53-66.
[12] ZHAO QY,ZHU ZL,XIAO WQ,et al.Hypoxia-induced circRNF13 promotes the progression and glycolysis of pancreatic cancer［J］.Exp Mol Med,2022,54(11):1940-1954.
[13] FICO F,SANTAMARIA-MARTINEZ A.TGFBI modulates tumour hypoxia and promotes breast cancer metastasis［J］.Mol Oncol,2020,14(12):3198-3210.
[14] GAO JC,FEI LX,WU XT,et al.MiR-766-3p suppresses malignant behaviors and stimulates apoptosis of colon cancer cells via targeting TGFBI［J］.Can J Gastroenterol Hepatol,2022,1(17):4-12.
[15] YANG RH,ZUO LK,MA H,et al.Downregulation of nc886 contributes to prostate cancer cell invasion and TGFβ1-induced EMT［J］.Genes Dis,2021,9(4):1086-1098.
[16] PARSONS MJ,TAMMELA T,DOW LE.WNT as a driver and dependency in cancer［J］.Cancer Discov,2021,11(10):2413-2429.
[17] ZHU LZ,TIAN Q,GAO H,et al.PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK［J］.Int J Biol Sci,2022,18(5):2032-2046.
[18] CAI K,DENG L,ZHENG DJ,et al.MICAL1 facilitates pancreatic cancer proliferation,migration,and invasion by activating WNT/β-catenin pathway［J］.J Transl Med,2022,20(1):528-545.
[19] PASTUSHENKO I,BLANPAIN C.EMT transition states during tumor progression and metastasis［J］.Trends Cell Biol,2019,29(3):212-226.
[20] TIAN S,PENG PL,LI J,et al.SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway［J］.Aging(Albany NY),2020,12(4):3574-3593.
[21] 庞翠，张菊，刘文超.EMT研究进展［J］.现代肿瘤医学，2016，24（15）：2484-2487. PANG C,ZHANG J,LIU WC.The research progression of EMT［J］.Modern Oncology,2016，24（15）：2484-2487.

Memo

Memo:
浙江省医药卫生科技项目(编号：2019RC132)
Last Update: 2023-11-30