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image of Targeting Telomere Shelterin Protein TPP1 with Elbasvir: Induction of Autophagy and Suppression of Esophageal Cancer Tumorigenesis
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Abstract

Introduction

Esophageal cancer often develops insidiously, with most cases diagnosed at an advanced stage. Currently, the pathogenesis of esophageal cancer remains unclear, treatment outcomes are poor, and the five-year survival rate is low. To tackle the significant clinical challenges of difficult diagnosis and unfavorable prognosis, it is crucial to actively investigate the disease's pathogenesis. This study explored the involvement of telomere shelterin protein TPP1 in the pathogenesis of esophageal cancer and identified potential therapeutic agents for its treatment.

Methods

The expression level of TPP1 protein in 54 pairs of esophageal cancer tissues and paired adjacent tissues was detected immunohistochemistry. The impact of TPP1 silencing and Elbasvir administration on the growth of KYSE150 and TE1 esophageal cancer cell lines was assessed utilizing Cell Counting Kit-8 and colony formation assays. Cell migration was assessed through Transwell and scratch assays. Fluorescence microscopy was employed to observe autophagosome formation, while flow cytometry measured the fluorescence intensity of autophagy markers LC3 and P62 in TPP1-silenced KYSE150 and TE1 cells. Western blotting was utilized to examine the alterations in TPP1, the AKT-mTOR signaling pathway, autophagy-related proteins, and other associated proteins.

Results

TPP1 levels were notably elevated in esophageal squamous cell carcinoma tissues relative to adjacent normal tissues. Suppression of TPP1 substantially reduced the growth and movement of esophageal cancer cells , while triggering autophagy the AKT-mTOR signaling pathway, highlighting TPP1’s cancer-promoting function in esophageal cancer.

Discussion

Elbasvir effectively suppressed the growth and spread of KYSE150 and TE1 cell lines , downregulating TPP1 protein expression in relation to time and dosage. Additional investigations revealed that Elbasvir also inhibited the AKT-mTOR signaling axis and induced autophagy by targeting TPP1. Notably, rescue experiments demonstrated that 3-MA could reverse the inhibitory effects on proliferation, migration, and autophagy induced by TPP1 silencing or Elbasvir treatment in KYSE150 and TE1 cells.

Conclusion

TPP1 emerges as a compelling diagnostic indicator and a potential treatment focus in esophageal cancer, with Elbasvir offering promise as a novel therapeutic agent.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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/content/journals/acamc/10.2174/0118715206393619250911115554
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Targeting Telomere Shelterin Protein TPP1 with Elbasvir: Induction of Autophagy and Suppression of Esophageal Cancer Tumorigenesis
Bentham Science Publishers ; https://doi.org/10.2174/0118715206393619250911115554
/content/journals/acamc/10.2174/0118715206393619250911115554
/content/journals/acamc/10.2174/0118715206393619250911115554
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  • Article Type:     Research Article
Keywords: AKT-mTOR ; elbasvir ; immunohistochemistry ; autophagy ; telomere shelterin protein ; Esophageal cancer

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