Salicylic Acid Inhibits Growth and Sensitizes Cervical Cancer Cells to Radiotherapy by Activating AMPK/TSC2/mTOR Pathway

Abstract

Background Radioresistance remains a major clinical challenge in cervical cancer therapy. Salicylic acid (SA)-mediated direct activation of AMP–activated protein kinase (AMPK) is critical to radiosensitivity. However, limited data exists regarding the combination of SA and radiotherapy, even though there are several indications that this might be a promising treatment strategy. This study aimed to investigate the radiosensitizing effect of SA on human cervical cancer cells and its potential molecular mechanism. Methods Cervical cancer cells were treated with SA and ionizing radiation. The expression of γ-H2AX was evaluated by immunofluorescence (IF) assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to detect the protein level of AMPK/TSC2/mTOR pathway. Results SA inhibited basal proliferation of cervical cancer cells in a dose and time dependent manner. In addition, SA increased radiation-induced DNA damage, promoted apoptosis, triggered a redistribution of cell cycle from G2-M phase to G1-S phase of cervical cancer cells, and hence increased cell sensitivity to radiation. Moreover, SA treatment elevated the expression levels of p-AMPKα and p-TSC2, whereas the level of p-mTOR was significantly decreased. Conclusion SA enhances the radiosensitivity of cervical cancer cells by targeting AMPK/TSC2/mTOR signaling pathway, and might serve as a promising therapeutic strategy to improve the efficacy of radiotherapy for cervical cancer.