Arenobufagin Enhances the Radiosensitivity of Cervical Cancer Cells by Inhibiting the NF-κB Signaling Pathway

Abstract

Radiotherapy is among the main methods for treating cervical cancer; however, its therapeutic effect is limited by radioresistance. Thus, identifying effective drugs to overcome radioresistance is necessary. Arenobufagin, a bufadienolide compound, has been shown to exhibit anticancer effects. The aim of this study was to clarify the effect of arenobufagin on the radiosensitivity of cervical cancer and to explore the potential molecular mechanisms. The roles of arenobufagin in the radiosensitivity of cervical cancer cells were examined using cytotoxicity assays, colony formation assays, scratch tests, apoptosis assays, comet assays, and mouse models. The cervical cancer cells were irradiated after treatment with arenobufagin, and the extracted proteins were concentrated using nanoabsorbent microspheres. Western blotting was used to detect the expression of NF-κB signal-related proteins in the proteins concentrated by nanoabsorbent microspheres. Arenobufagin inhibited cell proliferation, increased cell apoptosis, promoted DNA damage, and inhibited the growth of transplanted tumors; thus, the radiosensitivity of C33A cells was enhanced. Mechanistically, we found that arenobufagin enhanced radiosensitivity by inhibiting the NF-κB signaling pathway. In conclusion, this study demonstrated that arenobufagin enhanced the radiosensitivity of cervical cancer cells in vitro and in vivo. The underlying mechanism might involve the inhibition of cell viability, an increase in DNA damage, and the induction of cell apoptosis by inhibiting the NF-κB pathway.