Arsenic enhances cervical cancer cell radiosensitivity by suppressing the DNA damage repair pathway.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is a primary treatment for cervical cancer (CC) and combines chemotherapy and radiation therapy to target cancer cells effectively. However, despite its benefits, it also involves a high risk of recurrence and metastasis, partly due to the resistance of some cancer cells to the treatment. Additionally, CCRT can cause various treatment-related adverse reactions, such as gastrointestinal issues, bone marrow suppression, and skin reactions, which can negatively impact patients' quality of life. Therefore, there is a compelling need to develop more effective treatment strategies that can improve the outcomes of CCRT while minimizing its side effects. This study aimed to investigate the radiosensitizing effects of arsenic trioxide (ATO) on CC and explore its underlying molecular mechanisms. METHODS: We conducted both in vitro and in vivo experiments to evaluate the radio-sensitizing properties of ATO. The in vitro effects of ATO were assessed using clonogenic assay, while in vivo effects were evaluated using a xenograft model. Then cell viability, cell cycle, and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. RNA sequencing was performed to identify the differentially expressed genes. Finally, mRNA and protein expressions of key hub genes were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Western blot, immunofluorescence, and RNA sequencing analyzed molecular mechanisms. RESULTS: ATO significantly enhanced the radiosensitivity of CC cells, as evidenced by reduced colony formation in vitro and inhibited tumor growth in vivo. This enhancement was achieved by impairing the DNA damage repair pathway, specifically through the downregulation of key proteins such as breast cancer 1 (BRCA1) and bloom syndrome protein (BLM). Notably, overexpression of BRCA1 or BLM substantially mitigated ATO's radiosensitizing effects. CONCLUSIONS: This study demonstrates that ATO exhibits radiosensitizing effects on CC by inhibiting DNA damage repair. These findings provide theoretical and experimental support for using ATO as a radiosensitizer in CC therapy, potentially leading to improved treatment outcomes, reduced recurrence rates, and enhanced patient survival. Future research should focus on optimizing ATO's dosage and timing as well as evaluating its long-term safety and efficacy in clinical settings.