|Table of Contents|

Mechanism of chaetocin targeting Hsp90 to inhibit Eca109 proliferation in esophageal squamous carcinoma cells

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

Issue:
2023 15
Page:
2815-2822
Research Field:
Publishing date:

Info

Title:
Mechanism of chaetocin targeting Hsp90 to inhibit Eca109 proliferation in esophageal squamous carcinoma cells
Author(s):
JIANG Hangyu1; CHU Yueming1; LI Yuqi2; LI Lin3; LIU Kang4
1.School of Pharmacy,North Sichuan Medical College,Sichuan Nanchong 637000,China;2.Department of Pharmacy,Nanchong Traditional Chinese Medicine Hospital,Sichuan Nanchong 637000,China；3.Department of Pharmacy;4.Institute of Tissue Engineering and Stem Cells,The Second Clinical Medical College of North Sichuan Medical College,Sichuan Nanchong 637000,China.
Keywords:
chaetocin; ESCC; Hsp90 protein; proliferation; apoptosis; migration and invasion
PACS:
R735.1
DOI:
10.3969/j.issn.1672-4992.2023.15.010
Abstract:
Objective:To investigate the effects and mechanisms of chaetocin on cell proliferation,migration,invasion,cell cycle and apoptosis in esophageal squamous cell carcinoma(ESCC).Methods:After traeting Ecalog cells with different concentrations of chaetocin treatment Eca109 cells,CCK-8 assay,3D tumor spheroid formation assay,clone formation assay were applied to detect the influence of chaetocin on ESCC cells proliferation vitality.Flow cytometry was used to detect the influence of chaetocin on ESCC cell cycle and apoptosis.Wound healing assay and Transwell assay were applied to detect the influence of chaetocin on migration and invasion.Molecular docking and cellular thermal shift experiments verified the interaction between chaetocin and Hsp90.Cell cycle,apoptosis,migration and invasion and molecular mechanisms related protein were detected by immunoblotting.Results:Chaetocin significantly inhibited Eca109 cell survival and inhibited sphere-forming capacity and colony-forming capacity(P＜0.01).Flow cytometry results showed that the percentage of G2/M phase increased(P＜0.001) and apoptosis cells increased in chaetocin group,compared with control group(P＜0.01).The results of wound healing assay and Transwell showed that the migration and invasion of Eca109 cells were significantly reduced by chaetocin(P＜0.01).Molecular docking and cellular thermal shift experiments suggested that chaetocin has strong binding capacity to Hsp90.Western blot results showed that the cell cycle-related proteins CDK1 was decreased,p-Histone H3 was increased,apoptosis-related proteins Cleaved-PARP and Cleaved-caspase-3 were increased,migration and invasion-related proteins E-Cadherin was decreased,N-Cadherin and Snail were decreased,Hsp90 client proteins p-EGFR,p-STAT3,p-AKT and p-ERK1/2 were decreased.Conclusion：Chaetocin cloud suppress the proliferation of ESCC cell by targeting Hsp90 inhibit the activity of its client proteins.

References:

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Memo

Memo:
四川省中医药管理局中医药科研专项（编号：2020JC0082）
Last Update: 2023-06-30