Abstract
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.
Highlights
Esophageal cancer (EC) is one of the most common cancers worldwide, with the distribution of its histologic subtypes—esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA)—differing depending on geography (Siegel et al, 2020)
KYSE150 and KYSE450 cells were treated with PBS or FL to verify whether FL was related to ESCC tumor growth
To assess the effect of FL (200 ng/ml) on 8 Gy IR-induced DNA damage and repair in ESCC cells, we used immunofluorescence to detect the number of gamma-H2AX (γ-H2AX) at different time points (0, 2, 6, and 24 h) after FL administration in the ionizing radiation X-ray exposure group
Summary
Esophageal cancer (EC) is one of the most common cancers worldwide, with the distribution of its histologic subtypes—esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA)—differing depending on geography (Siegel et al, 2020). ESCC is a prevalent histological classification in East Asia (Colvin et al, 2017). Radiotherapy (RT) is recommended as an important and effective method for malignant treatment in about half of cancer patients during. FL Increase Radiorsistance in ESCC clinical treatment (Mariette et al, 2015). ESCC patients who have contraindications for surgery or locally advanced disease have a treatment option through RT.
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