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.

中文翻译：

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XAV939抑制Wnt信号通路可增强人类宫颈癌HeLa细胞的放射敏感性。

宫颈癌是威胁女性健康的第二大最常见的恶性肿瘤。近年来，重离子束治疗正成为一种新兴的癌症治疗手段。然而，抗辐射和辐射引起的损害构成了治疗宫颈癌的主要障碍。因此，鉴别放射增敏剂至关重要。在这里，我们调查了Wnt信号通路对HeLa细胞中12C6 +辐射响应的影响。在12C6 +辐射之前两小时添加了Wnt信号通路抑制剂XAV939.12C6 +辐射以时间依赖的方式抑制HeLa细胞的活力，使用XAV939抑制Wnt信号传导显着增强了这种压力。同时，12C6 +辐射诱导细胞凋亡显着增加，G2 / M期停滞，和γ-H2AX病灶的数量。XAV939的补充显着增加了仅由12C6 +辐射诱导的效应。XAV939与12C6 +照射相结合，凋亡基因（p53，Bax，Bcl-2）的表达显着增加，而Wnt相关基因（Wnt3a，Wnt5a，β-catenin，cyclin D1和c-Myc）的表达显着增加。减少了。总体而言，这些发现表明，Wnt /β-catenin途径的阻滞有效地使HeLa细胞对12C6 +辐射敏感，就提高12C6 +束的临床疗效而言，它可能是一种潜在的治疗方法。而Wnt相关基因（Wnt3a，Wnt5a，β-catenin，cyclin D1和c-Myc）的表达明显降低。总体而言，这些发现表明，Wnt /β-catenin途径的阻滞有效地使HeLa细胞对12C6 +辐射敏感，就提高12C6 +束的临床疗效而言，它可能是一种潜在的治疗方法。而Wnt相关基因（Wnt3a，Wnt5a，β-catenin，cyclin D1和c-Myc）的表达明显降低。总体而言，这些发现表明，Wnt /β-catenin途径的阻断可有效地使HeLa细胞对12C6 +辐射敏感，就提高12C6 +束的临床疗效而言，它可能是一种潜在的治疗方法。