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

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 C-12(6+) radiation in HeLa cells. XAV939, an inhibitor of Wnt signalling pathway, was added two hours before C-12(6+) radiation.C-12(6+) radiation inhibited the viability of HeLa cells in a time-dependent manner, and inhibiting Wnt signalling using XAV939 significantly intensified this stress. Meanwhile, C-12(6+) radiation induced a significant increased cell apoptosis, G2/M phase arrest, and the number of gamma-H2AX foci. Supplementation with XAV939 significantly increased the effects induced by C-12(6+) radiation alone. Combining XAV939 with C-12(6+) irradiation, the expression of apoptotic genes (p53, Bax, Bcl-2) was significantly increased, while the expression of Wnt-related genes (Wnt3a, Wnt5a, beta-catenin, cyclin D1 and c-Myc) was significantly decreased. Overall, these findings suggested that blockage of the Wnt/beta-catenin pathway effectively sensitizes HeLa cells to C-12(6+) irradiation, and it may be a potential therapeutic approach in terms of increasing the clinical efficacy of C-12(6+) beams.