Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells

Wnt信号通路 赫拉 辐射敏感性 细胞凋亡 癌症研究 WNT3A型 细胞周期蛋白D1 宫颈癌 癌症 化学 生物 细胞周期 分子生物学 信号转导 医学 放射治疗 细胞生物学 细胞 内科学 生物化学 遗传学
作者
Jinhua Zhang,Jing Si,Lu Gan,Menghuan Guo,Junfang Yan,Yuhong Chen,Fang Wang,Hong Zhang,Yupei Wang,Hong Zhang
出处
期刊:Artificial Cells Nanomedicine and Biotechnology [Informa]
卷期号:48 (1): 479-487 被引量:25
标识
DOI:10.1080/21691401.2020.1716779
摘要

Cervical cancer is the second most common malignant tumour threatening women's health. In recent years, heavy-ion beam therapy is becoming a newly emerging therapeutic mean of cancer; however, radio-resistance and radiation-induced damage constitute the main obstacles for curative treatment of cervical cancer. Therefore, to identify the radiosensitizers is essential. Here, we investigated the effects of Wnt signalling pathway on the response of 12C6+ radiation in HeLa cells. XAV939, an inhibitor of Wnt signalling pathway, was added two hours before 12C6+ radiation.12C6+ radiation inhibited the viability of HeLa cells in a time-dependent manner, and inhibiting Wnt signalling using XAV939 significantly intensified this stress. Meanwhile, 12C6+ radiation induced a significant increased cell apoptosis, G2/M phase arrest, and the number of γ-H2AX foci. Supplementation with XAV939 significantly increased the effects induced by 12C6+ radiation alone. Combining XAV939 with 12C6+ irradiation, the expression of apoptotic genes (p53, Bax, Bcl-2) was significantly increased, while the expression of Wnt-related genes (Wnt3a, Wnt5a, β-catenin, cyclin D1 and c-Myc) was significantly decreased. Overall, these findings suggested that blockage of the Wnt/β-catenin pathway effectively sensitizes HeLa cells to 12C6+ irradiation, and it may be a potential therapeutic approach in terms of increasing the clinical efficacy of 12C6+ beams.
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