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

Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):479-487. doi: 10.1080/21691401.2020.1716779.

Abstract

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.

Keywords: 12C6+ irradiation; Wnt/β-catenin pathway; XAV939; cervical carcinoma; radio-sensitivity.

Publication types

  • Video-Audio Media

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis* / drug effects
  • Apoptosis* / radiation effects
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • G2 Phase Cell Cycle Checkpoints / radiation effects
  • HeLa Cells
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Humans
  • M Phase Cell Cycle Checkpoints / drug effects
  • M Phase Cell Cycle Checkpoints / radiation effects
  • Neoplasm Proteins / metabolism
  • Radiation Tolerance* / drug effects
  • Radiation Tolerance* / radiation effects
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology
  • Uterine Cervical Neoplasms* / radiotherapy
  • Wnt Signaling Pathway* / drug effects
  • Wnt Signaling Pathway* / radiation effects

Substances

  • Apoptosis Regulatory Proteins
  • Heterocyclic Compounds, 3-Ring
  • Neoplasm Proteins
  • XAV939