|Table of Contents|

Effects of 5-fluorouracil and oxaliplatin on autophagy and exosome release of colon cancer cells and its mechanism

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

Issue:
2023 07
Page:
1226-1230
Research Field:
Publishing date:

Info

Title:
Effects of 5-fluorouracil and oxaliplatin on autophagy and exosome release of colon cancer cells and its mechanism
Author(s):
SHI Wen; HE Xiangfeng; CHEN Jinpeng; SUN Yongqiang; ZHOU Zhiqiang; CAI Ming; QIU Jian
Department of Thyroid and Breast Surgery,the Second Affiliated Hospital,Nantong University,Jiangsu Nantong 226001,China.
Keywords:
5-FU; oxaliplatin; colon adenocarcinoma cells; autophagy; exosomes
PACS:
R730.5
DOI:
10.3969/j.issn.1672-4992.2023.07.008
Abstract:
Objective:To investigate the effects of 5-fluorouracil(5-FU) and oxaliplatin on autophagy and exosome release of mouse colon adenocarcinoma CT26.WT cells and the correlation mechanism between them.Methods:Western blot was used to detect the expression of autophagy related protein and exocytosis regulatory protein Syntaxin in CT26.WT cells treated with normal culture,5-FU,oxaliplatin and starvation culture.After normal culture,5-FU,oxaliplatin and starvation culture,the relative position relationship between multivesicles and autophagosomes and between multivesicles and lysosomes in CT26.WT cells were detected by confocal laser scanning microscope(CLSM).The exosomes in the culture supernatant of cells in each group were extracted by differential hypervelocity centrifugation,and the expression of Syntaxin and exosome marker protein were detected by Western blot.Results:5-FU,oxaliplatin and starvation treated CT26.WT cells could induce autophagy.Under CLSM,some polyvesicles and autophagosomes coincided,and some polyvesicles coincided with lysosomes.After starvation culture,the expression of syntaxin in CT26.WT cells was lower than that in the normal control group.After treatment with 5-FU or oxaliplatin,the expression of Syntaxin protein had no significant change compared with that in the normal control group.The expression of EGFP-CD63 protein in exosomes of 5-FU and oxaliplatin treatment group was significantly lower than that of normal control group.Conclusion:5-FU and oxaliplatin do not affect the formation of multivesicles in CT26.WT cells,but can induce autophagy in CT26.WT cells and promote the degradation of multivesicles through autophagy lysosomal pathway,so as to down regulate the release of exosomes.

References:

［1］LISA NIELAND,LIZA M MORSETT,MARIKE LD BROEKMAN,et al.Extracellular vesicle-mediated bilateral communication between glioblastoma and astrocytes［J］.Trends Neurosci,2021,44(3):215-226.
［2］LI KY,CHEN YH,LI A,et al.Exosomes play roles in sequential processes of tumor metastasis［J］.Int J Cancer,2019,144(7):1486-1495.
［3］LAURA POILLET-PEREZ,XIE XQ,ZHAN L, et al.Autophagy maintains tumour growth through circulating arginine［J］.Nature,2018,563(7732):569-573.
［4］RAGHU KALLURI,VALERIE S LEBLEU.The biology,function,and biomedical applications of exosomes［J］.Science,2020,367(6478):eaau6977.
［5］ZHANG L,YU DH.Exosomes in cancer development,metastasis,and immunity［J］.Biochim Biophys Acta Rev Cancer,2019,1871(2):455-468.
［6］CLAUDE-TAUPIN A,JIA J,MUDD M,et al.Autophagy's secret life:secretion instead of degradation［J］.Essays Biochem,2017,61(6):637-647.
［7］CADWELL K,DEBNATH J.Beyond self-eating:the control of nonautophagic functions and signaling pathways by autophagyrelated proteins［J］.J Cell Biol,2018,217(3):813-822.
［8］XU J,ROBERT CAMFIELD,SHARON M GORSKI.The interplay between exosomes and autophagy-partners in crime［J］.J Cell Sci,2018,131(15):jcs215210.
［9］GAO J,WEI B,DE ASSUNCAO TM,et al.Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis［J］.J Hepatol,2020,73(5):1144-1154.
［10］GEORGIA MINAKAKI,STEFANIE MENGES,AGNES KITTEL,et al.Autophagy inhibition promotes SNCA/alpha-synuclein release and transfer via extracellular vesicles with a hybrid autophagosome-exosome-like phenotype［J］.Autophagy,2018,14(1):98-119.
［11］YAN SY,ZHOU N,ZHANG DR, et al.PFKFB3 inhibition attenuates oxaliplatin-induced autophagy and enhances its cytotoxicity in colon cancer cells［J］.Int J Mol Sci,2019,20(21):5415.
［12］MA LJ,WANG YH.JAK2/STAT3 inhibitor reduced 5-FU resistance and autophagy through ATF6-mediated ER stress［J］.J Recept Signal Transduct Res,2021,18:1-8.
［13］MRIGYA BABUTA,ISTVAN FURI,SHASHI BALA,et al.Dysregulated autophagy and lysosome function are linked to exosome production by microRNA 155 in alcoholic liver disease［J］.Hepatology,2019,70(6):2123-2141.
［14］ZHANG XW,ZHOU JC,PENG D,et al.Disrupting the TRIB3-SQSTM1 interaction reduces liver fibrosis by restoring autophagy and suppressing exosome-mediated HSC activation［J］.Autophagy,2020,16(5):782-796.
［15］MARTINA RAUDENSKA,JAN BALVAN,MICHAL MASARIK.Crosstalk between autophagy inhibitors and endosome-related secretory pathways:a challenge for autophagy-based treatment of solid cancers［J］.Mol Cancer,2021,20(1):140.
［16］WANG YX,LI YZ,ZHOU H,et al.Syntaxin 2 promotes colorectal cancer growth by increasing the secretion of exosomes［J］.J Cancer,2021,12(7):2050-2058.
［17］BOR LUEN TANG.Syntaxin 16's newly deciphered roles in autophagy［J］.Cells,2019,8(12):1655.

Memo

Memo:
中国博士后科学基金面上资助项目（编号：2013M530227）;江苏省博士后科研资助计划（编号：1301099C）；江苏省南通市科学技术局项目（编号：BK2012067，HS2013031）;江苏省南通市卫健委面上项目（编号：MB2020008）
Last Update: 2023-02-28