Gao Xingxing, Liu Genyun, Zhao Zimu, Tang Yi, Hui Hui, Wang Chaoqun, Li Danhua, Ma Yu, Sun Zhuo, Zhou Yun
The Affiliated Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, China.
Department of Pathology, School of Basic Medical Sciences, Xuzhou Key Laboratory of Clinical and Experimental Pathology, Xuzhou Medical University, Xuzhou, China.
Transl Cancer Res. 2025 Mar 30;14(3):2078-2094. doi: 10.21037/tcr-2025-450. Epub 2025 Mar 27.
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.
We conducted both and experiments to evaluate the radio-sensitizing properties of ATO. The effects of ATO were assessed using clonogenic assay, while 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.
ATO significantly enhanced the radiosensitivity of CC cells, as evidenced by reduced colony formation and inhibited tumor growth . This enhancement was achieved by impairing the DNA damage repair pathway, specifically through the downregulation of key proteins such as breast cancer 1 () and bloom syndrome protein (). Notably, overexpression of BRCA1 or BLM substantially mitigated ATO's radiosensitizing effects.
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.
同步放化疗（CCRT）是宫颈癌（CC）的主要治疗方法，它将化疗和放疗结合起来以有效靶向癌细胞。然而，尽管其有诸多益处，但它也存在较高的复发和转移风险，部分原因是一些癌细胞对该治疗产生耐药性。此外，同步放化疗会引发各种与治疗相关的不良反应，如胃肠道问题、骨髓抑制和皮肤反应，这些会对患者的生活质量产生负面影响。因此，迫切需要开发更有效的治疗策略，既能改善同步放化疗的疗效，又能将其副作用降至最低。本研究旨在探究三氧化二砷（ATO）对宫颈癌的放射增敏作用，并探索其潜在的分子机制。
我们进行了体外和体内实验以评估ATO的放射增敏特性。使用克隆形成试验评估ATO的体外作用，而使用异种移植模型评估体内作用。然后通过细胞计数试剂盒 - 8（CCK - 8）试验和流式细胞术评估细胞活力、细胞周期和凋亡。进行RNA测序以鉴定差异表达基因。最后，通过定量实时聚合酶链反应（qRT - PCR）和蛋白质印迹分析关键枢纽基因的mRNA和蛋白质表达。通过蛋白质印迹、免疫荧光和RNA测序分析分子机制。
ATO显著增强了宫颈癌细胞的放射敏感性，克隆形成减少和肿瘤生长受抑制证明了这一点。这种增强是通过损害DNA损伤修复途径实现的，具体是通过下调关键蛋白如乳腺癌1（BRCA1）和布鲁姆综合征蛋白（BLM）。值得注意的是，BRCA1或BLM的过表达显著减轻了ATO的放射增敏作用。
本研究表明ATO通过抑制DNA损伤修复对宫颈癌具有放射增敏作用。这些发现为将ATO用作宫颈癌治疗中的放射增敏剂提供了理论和实验支持，可能会改善治疗效果、降低复发率并提高患者生存率。未来的研究应专注于优化ATO的剂量和给药时间，以及评估其在临床环境中的长期安全性和疗效。
