|Table of Contents|

Thioredoxin interacting protein promotes the occurrence of colon adenocarcinoma cell apoptosis by inhibiting autophagy pathway

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

Issue:
2022 03
Page:
395-401
Research Field:
Publishing date:

Info

Title:
Thioredoxin interacting protein promotes the occurrence of colon adenocarcinoma cell apoptosis by inhibiting autophagy pathway
Author(s):
ZHANG Lifang1YANG Jielin2HU Xiaoli2XU Jiang1
1.Department of Internal Medicine,Qinhuangdao Orthopedic Hospital,Hebei Qinhuangdao 066001,China;2.Department of Gastroenterology,the First Affiliated Hospital of Hebei North University,Hebei Zhangjiakou 075000,China.
Keywords:
colon adenocarcinomathioredoxin interacting proteinapoptosisautophagy
PACS:
R735.3+5
DOI:
10.3969/j.issn.1672-4992.2022.03.006
Abstract:
Objective:To explore the effect and mechanism of overexpression of thioredoxin interacting protein(TXNIP) on the apoptosis of colon adenocarcinoma cells.Methods:Collect colon adenocarcinoma and paracancerous tissues from 30 patients with colon adenocarcinoma in our hospital.Real-time fluorescence quantitative PCR detected the expression of TXNIP mRNA in the tissue.Immunohistochemical staining was used to detect the expression of autophagy marker protein LC3-Ⅱ and apoptosis marker protein Cleaved Caspase-3 in tissues.Human colon adenocarcinoma LoVo cells were randomly divided into control group,negative empty vector group(LV-GFP) and TXNIP overexpression group(LV-GFP-TXNIP).Observe cell transfection efficiency under an inverted fluorescence microscope.Collect LoVo cells 72 h after transfection,detect cell apoptosis by flow cytometry.Transmission electron microscope observes the autophagy of cells.Immunofluorescence staining detected the expression of LC3 in cells.Western blot was used to detect changes in the expression of autophagy-related proteins and apoptosis-related proteins in cells.Results:Compared with adjacent tissues,the relative expression of TXNIP mRNA in the colon adenocarcinoma tumor tissue was significantly decreased(P<0.01),the positive expression rate of LC3-Ⅱ was significantly increased(P<0.05),and the positive expression rate of Cleaved Caspase-3 significantly reduced(P<0.05).72 h after lentivirus transfection,the transfection efficiency was higher(P<0.05).Compared with the control group,the apoptosis rate of LoVo cells in the LV-GFP-TXNIP group was significantly increased(P<0.05),the cytoplasm was denser,the number of autophagosomes was significantly reduced,the fluorescence staining of LC3 was weakened,and the expression of Beclin-1 and LC3-Ⅱ proteins significantly decreased(P<0.05),while the expression of LC3-I and p62 protein increased significantly(P<0.05).At the same time,the protein expression of Bax and Cleaved Caspase-3 increased significantly(P<0.05),and the protein expression of Bcl-2 decreased significantly(P<0.05).Conclusion:Overexpression of TXNIP in colon adenocarcinoma cells can promote apoptosis by inhibiting autophagy.

References:

[1] MILIKO M,YUICHIRO H,YUKO I,et al.Metastatic colon cancer of the small intestine diagnosed using genetic analysis:a case report[J].Diagn Pathol,2020,15(1):1786-1792.
[2] MOFAN G,SUSAN T.Colorectal cancer in the United States and a review of its heterogeneity among Asian American subgroups[J].Asia-Pac J Clin Onco,2020,16(4):193-200.
[3] NICOLAS DG,MARIE-ALICE M,EDOUARD L,et al.Specificity of metabolic colorectal cancer biomarkers in serum through effect size[J].Metabolomics,2020,16(8):683-691.
[4]陈海东.结直肠癌患者的临床诊疗进展[J].吉林医学,2020,41(8):1965-1966. CHEN HD.Progress in clinical diagnosis and treatment of patients with colorectal cancer[J].Jilin Medical Journal,2020,41(8):1965-1966.
[5] RODRIGUEZ-GARCIA A,HEVIA D,MAYO JC,et al.Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells[J].Redox Biol,2017,12(8):634-647.
[6] ARIANA ES,LUIZ F DE S,BARBARA DOS S,et al.Methylglyoxal-induced protection response and toxicity:Role of glutathione reductase and thioredoxin systems[J].Neurotox Res,2017,32(3):340-350.
[7] ALISON D,CATHERINE BV,PERRINE MR,et al.Targeting endothelial thioredoxin-interacting protein(TXNIP) protects from metabolic disorder-related impairment of vascular function and post-ischemic revascularisation[J].Angiogenesis,2020,23(2):249-264.
[8] ERTA K,SEBASTIAN M,ANNE HR.Immune-modulating effects of conventional therapies in colorectal cancer[J].Cancers,2020,12(8):2193.
[9] SHAH A,XIA L,MASSON EA,et al.Thioredoxin-interacting protein deficiency protects against diabetic nephropathy[J].J Am Soc Nephrol,2015,26(12):2963-2977.
[10] SONG S,QIU D,WANG Y,et al.TXNIP deficiency mitigates podocyte apoptosis via restraining the activation of mTOR or p38 MAPK signaling in diabetic nephropathy[J].Exp Cell Res,2020,388(2):111862.
[11]莫与琳,杨亚军,崔燎.TXNIP介导的氧化应激在疾病中的作用机制[J].中国药理学通报,2018,34(1):16-19. MO YL,YANG YJ,CUI L.Action and mechanism of oxidative stress mediated by TXNIP in diseases[J].Chinese Pharmacological Bulletin,2018,34(1):16-19.
[12]NIE W,HUANG W,ZHANG W,et al.TXNIP interaction with the Her-1/2 pathway contributes to overall survival in breast cancer[J].Oncotarget,2015,6(5):3003-3014.
[13]KANAJI N,KAMITORI K,HOSSAIN A,et al.Additive antitumour effect of Dallose in combination with cisplatin in non-small cell lung cancer cells[J].Oncol Rep,2018,39(3):1292-1298.
[14] PENG Y,QIU L,XU D,et al.M4IDP,a zoledronic acid derivative,induces G1 arrest,apoptosis and autophagy in HCT116 colon carcinoma cells via blocking PI3K/Akt/mTOR pathway[J].Life Sci,2017,185(9):63-72.
[15] 邓正亭,李湧健,程彬彬.自噬与凋亡的相互关系在肿瘤方面的研究进展[J].现代肿瘤医学,2015,23(10):1467-1471. DENG ZT,LI YJ,CHENG BB.Research progresses on the relationship between autophagy and apoptosis in tumor[J].Modern Oncology,2015,23(10):1467-1471.
[16] ZHANG N,PENG F,WANG Y,et al.Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/ JNK signaling axis[J].Int J Biol Sci,2020,16(1):147-161.
[17] LI X,CHEN F,KANG J,et al.Stereoselective assembly of multifunctional spirocyclohexene pyrazolones that induce autophagy-dependent apoptosis in colorectal cancer cells[J].J Organomet Chem,2019,84(14):9138-9150.
[18] WANG Y,LUO Q,HE X,et al.Emodin induces apoptosis of colon cancer cells via induction of autophagy in a ROS-dependent manner[J].Oncol Res,2017,26(11):889-899.
[19] NAGAPPAN A,LEE WS,YUN JW,et al.Tetraarsenic hexoxide induces G2/M arrest,apoptosis,and autophagy via PI3K/Akt suppression and p38 MAPK activation in SW620 human colon cancer cells[J].PLoS One,2017,12(3):e0174591.
[20] ZHENG Y,TAN K,HUANG H.Long noncoding RNA HAGLROS regulates apoptosis and autophagy in colorectal cancer cells via sponging miR-100 to target ATG5 expression[J].J Cell Biochem,2019,120(3):3922-3933.

Memo

Memo:
河北省卫健委青年科技课题(编号:20190874)
Last Update: 2021-12-31