FMS-Related Tyrosine Kinase 3 Ligand Promotes Radioresistance in Esophageal Squamous Cell Carcinoma

Aim: The FMS-related tyrosine kinase 3 ligand (FL) has an important role in regulating FMS-related tyrosine kinase 3 (Flt-3) activity. Serum FL levels are markedly increased among patients with hematopoietic disease. However, its role in radiation treatment remains unclear. In this study, we investi...

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Main Authors: Zuoquan Zhu, Jiahang Song, Junjie Gu, Bing Xu, Xinchen Sun, Shu Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.659735/full
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author Zuoquan Zhu
Jiahang Song
Junjie Gu
Bing Xu
Xinchen Sun
Shu Zhang
Shu Zhang
author_facet Zuoquan Zhu
Jiahang Song
Junjie Gu
Bing Xu
Xinchen Sun
Shu Zhang
Shu Zhang
author_sort Zuoquan Zhu
collection DOAJ
description Aim: The FMS-related tyrosine kinase 3 ligand (FL) has an important role in regulating FMS-related tyrosine kinase 3 (Flt-3) activity. Serum FL levels are markedly increased among patients with hematopoietic disease. However, its role in radiation treatment remains unclear. In this study, we investigated the effects of FL on radiotherapy for esophageal squamous cell carcinoma (ESCC).Methods: KYSE150 and KYSE450 cells were stimulated with FL (200 ng/ml). mRNA expression was analyzed using qRT-PCR. Cell viability was checked using CCK-8 assay kits. Proliferation was determined using the EdU assay. Radiosensitivity was detected through a colony-forming assay. Flow cytometry was used to evaluate cell apoptosis. The number of γH2AX foci was verified using an immunofluorescence assay. The change in relative proteins was determined by western blot analysis. The growth of transplanted tumors was demonstrated in nude mice.Results: Our results showed that FL increased the radiation resistance of ESCC cells by promoting clone formation, increasing EdU incorporation, enhancing DNA damage repair, and inhibiting apoptosis. Moreover, the Flt-3 receptor expression significantly increased in ESCC cells after radiation, which may have been an important factor in their radioresistance.Conclusion: Our results suggest that FL increases the radioresistance of esophageal cancer cells and that FL-Flt-3 could be a potential target for enhancing radiosensitivity in ESCC.
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spelling doaj.art-cf779be165af4cd3bed89027b243afb42022-12-21T20:25:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.659735659735FMS-Related Tyrosine Kinase 3 Ligand Promotes Radioresistance in Esophageal Squamous Cell CarcinomaZuoquan Zhu0Jiahang Song1Junjie Gu2Bing Xu3Xinchen Sun4Shu Zhang5Shu Zhang6Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaCore Facility Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaAim: The FMS-related tyrosine kinase 3 ligand (FL) has an important role in regulating FMS-related tyrosine kinase 3 (Flt-3) activity. Serum FL levels are markedly increased among patients with hematopoietic disease. However, its role in radiation treatment remains unclear. In this study, we investigated the effects of FL on radiotherapy for esophageal squamous cell carcinoma (ESCC).Methods: KYSE150 and KYSE450 cells were stimulated with FL (200 ng/ml). mRNA expression was analyzed using qRT-PCR. Cell viability was checked using CCK-8 assay kits. Proliferation was determined using the EdU assay. Radiosensitivity was detected through a colony-forming assay. Flow cytometry was used to evaluate cell apoptosis. The number of γH2AX foci was verified using an immunofluorescence assay. The change in relative proteins was determined by western blot analysis. The growth of transplanted tumors was demonstrated in nude mice.Results: Our results showed that FL increased the radiation resistance of ESCC cells by promoting clone formation, increasing EdU incorporation, enhancing DNA damage repair, and inhibiting apoptosis. Moreover, the Flt-3 receptor expression significantly increased in ESCC cells after radiation, which may have been an important factor in their radioresistance.Conclusion: Our results suggest that FL increases the radioresistance of esophageal cancer cells and that FL-Flt-3 could be a potential target for enhancing radiosensitivity in ESCC.https://www.frontiersin.org/articles/10.3389/fphar.2021.659735/fullfms-related tyrosine kinase 3 ligandesophageal squamous cell carcinomaapoptosisradiotherapyDNA damage
spellingShingle Zuoquan Zhu
Jiahang Song
Junjie Gu
Bing Xu
Xinchen Sun
Shu Zhang
Shu Zhang
FMS-Related Tyrosine Kinase 3 Ligand Promotes Radioresistance in Esophageal Squamous Cell Carcinoma
Frontiers in Pharmacology
fms-related tyrosine kinase 3 ligand
esophageal squamous cell carcinoma
apoptosis
radiotherapy
DNA damage
title FMS-Related Tyrosine Kinase 3 Ligand Promotes Radioresistance in Esophageal Squamous Cell Carcinoma
title_full FMS-Related Tyrosine Kinase 3 Ligand Promotes Radioresistance in Esophageal Squamous Cell Carcinoma
title_fullStr FMS-Related Tyrosine Kinase 3 Ligand Promotes Radioresistance in Esophageal Squamous Cell Carcinoma
title_full_unstemmed FMS-Related Tyrosine Kinase 3 Ligand Promotes Radioresistance in Esophageal Squamous Cell Carcinoma
title_short FMS-Related Tyrosine Kinase 3 Ligand Promotes Radioresistance in Esophageal Squamous Cell Carcinoma
title_sort fms related tyrosine kinase 3 ligand promotes radioresistance in esophageal squamous cell carcinoma
topic fms-related tyrosine kinase 3 ligand
esophageal squamous cell carcinoma
apoptosis
radiotherapy
DNA damage
url https://www.frontiersin.org/articles/10.3389/fphar.2021.659735/full
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