|Table of Contents|

Melatonin increases the sensitivity of esophageal cancer cells to paclitaxel by inhibiting the expression of ESCCAL-1

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

Issue:
2025 02
Page:
186-193
Research Field:
Publishing date:

Info

Title:
Melatonin increases the sensitivity of esophageal cancer cells to paclitaxel by inhibiting the expression of ESCCAL-1
Author(s):
ZHANG JingZHANG YueliGUAN HongyaLIU Jia
Zhengzhou Central Hospital Affiliated to Zhengzhou University,Henan Zhengzhou 450007,China.
Keywords:
melatoninesophageal cancerpaclitaxelESCCAL-1
PACS:
R735.1
DOI:
10.3969/j.issn.1672-4992.2025.02.004
Abstract:
Objective:To investigate the effect of melatonin on enhancing sensitivity of esophageal cancer cells to paclitaxel and its mechanism.Methods:Different concentrations of melatonin and paclitaxel were used to treat esophageal cancer cells separately or in combination.The changes of cell proliferation were analyzed by CCK-8 assay and clonogenesis assay.The expression of lncRNA ESCCAL-1 was detected by RT-qPCR.Western blot analysis was used to detect p-AKT,c-MYC,Bcl-2 and ULK1 protein levels.Results:Melatonin inhibited the activity of esophageal cancer cells in a dose-dependent manner (P<0.05).Melatonin increased the inhibitory effect of paclitaxel on EC-9706 and EC-109 cells (P<0.05),and decreased its IC50 value (P<0.01).The expression of ESCCAL-1 was inhibited by 0.5~2 mmol/L of melatonin (P<0.01),and overexpression of ESCCAL-1 reversed the effect of melatonin on paclitaxel.Melatonin inhibited the activation of AKT pathway,down-regulated the levels of protein c-MYC and Bcl-2,and up-regulated the level of protein ULK1.However,overexpression of ESCCAL-1 reversed the effects of melatonin on the expression of AKT pathway and related proteins.Conclusion:Melatonin inhibits the AKT pathway and cells proliferation by decreasing the expression of ESCCAL-1,and thereby increases the sensitivity of esophageal cancer cells to paclitaxel.

References:

[1]SIEGEL RL,GIAQUINTO AN,JEMAL A.Cancer statistics,2024[J].CA Cancer J Clin,2024,74(1):12-49.
[2]MOODY S,SENKIN S,ISLAM S,et al.Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence [J].Nat Genet,2021,53(11):1553-1563.
[3]HE Z,KE Y.Precision screening for esophageal squamous cell carcinoma in China [J].Chin J Cancer Res,2020,32(6):673-682.
[4]JING Z,CHEN K,GONG L.The significance of exosomes in pathogenesis,diagnosis,and treatment of esophageal cancer [J].Int J Nanomedicine,2021,16:6115-6127.
[5]SHEIKH M,ROSHANDEL G,MCCORMACK V,et al.Current status and future prospects for esophageal cancer [J].Cancers (Basel),2023,15(3):765.
[6]TALIB WH,ALSAYED AR,ABUAWAD A,et al.Melatonin in cancer treatment:Current knowledge and future opportunities [J].Molecule,2021,26(9):2506.
[7]MORTEZAEE K,POTES Y,MIRTAVOOS-MAHYARI H,et al.Boosting immune system against cancer by melatonin:A mechanistic viewpoint [J].Life Sci,2019,238:116960.
[8]TALIB WH.A ketogenic diet combined with melatonin overcomes cisplatin and vincristine drug resistance in breast carcinoma syngraft [J].Nutrition,2020,72:110659.
[9]CAO W,WU W,SHI F,et al.Integrated analysis of long noncoding RNA and coding RNA expression in esophageal squamous cell carcinoma [J].Int J Genomics,2013,2013:480534.
[10]LIU J,MAYEKAR MK,WU W,et al.Long non-coding RNA ESCCAL-1 promotes esophageal squamous cell carcinoma by down regulating the negative regulator of APOBEC3G [J].Cancer Lett,2020,493:217-227.
[11]MAFI A,KESHAVARZMOTAMED A,HEDAYATI N,et al.Melatonin targeting non-coding RNAs in cancer:Focus on mechanisms and potential therapeutic targets [J].Eur J Pharmacol,2023,950:175755.
[12]SAMLI H,SAMLI M,VATANSEVER B,et al.Paclitaxelresistance and the role of miRNAs in prostate cancer cell lines [J].World J Urol,2019,37(6):1117-1126.
[13]DANA PM,SADOUGHI F,MOBINI M,et al.Molecular and biological functions of melatonin in endometrial cancer [J].Curr Drug Targets,2020,21(5):519-526.
[14]MA ZQ,FENG YT,GUO K,et al.Melatonin inhibits ESCC tumor growth by mitigating the HDAC7/β-catenin/c-Myc positive feedback loop and suppressing the USP10-maintained HDAC7 protein stability [J].Mil Med Res,2022,9(1):54.
[15]GONG YQ,HOU FT,XIANG CL,et al.The mechanisms and roles of melatonin in gastrointestinal cancer [J].Front Oncol,2022,12:1066698.
[16]ERDOGAN CS,AL HASSADI Y,ARU B,et al.Combinatorial effects of melatonin and paclitaxel differ depending on the treatment scheme in colorectal cancer in vitro [J].Life Sci,2022,308:120927.
[17]秦文兵,张月丽,刘嘉,等.褪黑素通过调控EZH2表达增强食管癌细胞对5-氟尿嘧啶的敏感性[J].实用医学杂志,2021,37(2):188-194. QIN WB,ZHANG YL,LIU J,et al.Melatonin enhances the sensitivity of esophageal cancer cells to 5-fluorouracil by regulating EZH2 expression[J].Journal of Practical Medicine,2021,37(2):188-194.
[18]DINCER B,YILDIZTEKIN G,CINAR I.Unlocking synergistic potential:Agomelatine enhances the chemotherapeutic effect of paclitaxel in breast cancer cell through MT1 melatonin receptors and ER-alpha axis [J].Chem Biodivers,2023,20(10):e202301093.
[19]XIANG S,DAUCHY RT,HOFFMAN AE,et al.Epigenetic inhibition of the tumor suppressor ARHI by light at night-induced circadian melatonin disruption mediates STAT3-driven paclitaxel resistance in breast cancer [J].J Pineal Res,2019,67(2):e12586.
[20]LEE H,LEE HJ,JUNG JH,et al.Melatonin disturbs SUMOylation-mediated crosstalk between c-Myc and nestin via MT1 activation and promotes the sensitivity of paclitaxel in brain cancer stem cells [J].J Pineal Res,2018,65(2):e12496.
[21]GAO SC,WU MD,ZHANG XX,et al.Identification of prognostic melatonin-related lncRNA signature in tumor immune microenvironment and drug resistance for breast cancer [J].Asian J Surg,2023,46(9):3529-3541.
[22]LI Y,ZOU J,LI B,et al.Anticancer effects of melatonin via regulating lncRNA JPX-Wnt/β-catenin signalling pathway in human osteosarcoma cells [J].J Cell Mol Med,2021,25(20):9543-9556.
[23]YAN S,DU L,JIANG X,et al.Evaluation of serum exosomal lncRNAs as diagnostic and prognostic biomarkers for esophageal squamous cell carcinoma [J].Cancer Manag Res,2020,12:9753-9763.
[24]CUI Y,YAN M,WU W,et al.ESCCAL-1 promotes cell-cycle progression by interacting with and stabilizing galectin-1 in esophageal squamous cell carcinoma [J].NPJ Precis Oncol,2022,6(1):12.
[25]GUAN H,LV P,HAN P,et al.Long non-coding RNA ESCCAL-1/miR-590/LRP6 signaling pathway participates in the progression of esophageal squamous cell carcinoma[J].Cancer Med,2023,12(1):445-458.
[26]DONG Y,CAO X,HUANG J,et al.Melatonin inhibits fibroblast cell functions and hypertrophic scar formation by enhancing autophagy through the MT2 receptor-inhibited PI3K/Akt/mTOR signaling [J].Biochim Biophys Acta Mol Basis Dis,2024,1870(1):166887.

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河南省重点研发与推广专项(科技攻关)(编号:222102310107,232102311058);河南省医学科技攻关计划省部共建项目(编号:SBGJ202103101);河南省高校重点科研项目(编号:23A310025,23A310022)
Last Update: 1900-01-01