Abstract
Radiation therapy is an important component of the comprehensive treatment of esophageal cancer. However, conventional radiation resistance is one of the main reasons for treatment failure. The superiority of heavy ion radiation in physics and biology has been increasingly highlighted in radiation therapy research. The Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway plays an important role in the occurrence, development and metastasis of esophageal squamous cell carcinoma (ESCC) and is related to the development of resistance to ionizing radiation in ESCC. Therefore, the aim of the present study was to investigate the relationship between carbon ion inhibition of the proliferation and metastasis of esophageal carcinoma cells and the JAK2/STAT3 signaling pathway. The results demonstrated that carbon ion beams significantly reduced cell viability and stimulated apoptosis in human ESCC cells in a dose-dependent manner. In addition, carbon ion beams induced G2/M phase cell cycle arrest in ESCC cells and inhibited tumor metastasis in a dose-dependent manner. Additionally, poorly differentiated KYSE150 cells were more sensitive to the same carbon ion beam dose than moderately differentiated ECA109 cells. Carbon ion beam exposure regulated the relative expression of metastasis-related molecules at the transcriptional and translational levels in ESCC cells. Carbon ion beams also regulated CDH1 and MMP2 downstream of the STAT3 pathway and inhibited ESCC cell metastasis, which activated the STAT3 signaling pathway. This study confirmed the inhibition of cell proliferation and the metastatic effect of carbon ion beam therapy in ESCC cells.
Highlights
Esophageal cancer is the eighth most prevalent cancer worldwide and is the sixth leading cause of tumor-related death [1]
After 1 Gy irradiation, ECA109 and KYSE150 cell proliferation was significantly inhibited at 24 h, and this inhibition increased in a dose-dependent manner; ECA109 cell proliferation inhibition showed a decreasing trend at different times after irradiation, but no significant differences were found among the various time points (Figures 1D,E)
The treatment of esophageal squamous cell carcinoma (ESCC) is generally limited to surgical resection, chemotherapy and radiotherapy approaches, but the results are often largely unsatisfactory [6]
Summary
Esophageal cancer is the eighth most prevalent cancer worldwide and is the sixth leading cause of tumor-related death [1]. Radiation therapy is one of the mainstays of treatment for esophageal cancer, but in China, 95% of esophageal cancers are esophageal squamous cell carcinomas (ESCCs) [2]. Not many mechanisms by which carbon ion radiation induces tumor cell apoptosis and inhibits metastasis have been established. Signal transducer and activator of transcription 3 (STAT3) was recognized as an oncogene for its role in the malignant transformation of cells and tumorigenesis [3, 4]. STAT3 protein is activated by tyrosine phosphorylation at residue 705, and p-STAT3 (Tyr705) is able to upregulate the transcription of genes involved in cell proliferation, apoptosis, angiogenesis, invasion and metastasis. The mechanisms by which carbon ion beams function remain unclear, especially in terms of how they regulate the JAK2/STAT3 signaling pathway
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