LTB4R inhibits apoptosis and induces radiosensitivity by promoting the PI3K/AKT pathway in esophageal squamous cell carcinoma.

BACKGROUND

Radiotherapy (RT) is a critical treatment modality for esophageal squamous cell carcinoma (ESCC), yet radioresistance poses a major clinical challenge. Prior studies have reported elevated leukotriene B4 receptor (LTB4R) expression in ESCC tissues versus adjacent normal tissues, where it promotes cell proliferation, invasion, and metastasis. However, the correlation between LTB4R expression and ESCC radioresponsiveness remains uninvestigated. This study aimed to clarify LTB4R's role in regulating ESCC cell sensitivity to RT and its underlying molecular mechanisms.

METHODS

In vitro, Cell Counting Kit-8 (CCK-8), colony formation, scratch, and Transwell assays evaluated LTB4R's effects on ESCC cell proliferation, migration, and invasion post-RT. In vivo, subcutaneous xenograft models were established; mice were stratified into RT and non-RT groups, with immunohistochemistry (IHC) and hematoxylin-eosin (HE) staining to assess LTB4R's function. Transcriptome sequencing identified downstream pathways, which were validated via flow cytometry and Western blot.

RESULTS

LTB4R knockdown suppressed malignant phenotypes of ESCC cells after RT in vitro. Combined LTB4R inhibition and RT significantly reduced tumor volume in vivo, enhancing therapeutic efficacy. Mechanistically, LTB4R modulated ESCC radiosensitivity by activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and apoptotic signaling pathways.

CONCLUSIONS

LTB4R regulates ESCC radioresponse via the PI3K/AKT-apoptosis axis, and holds potential as a predictive biomarker for RT efficacy in ESCC.