AI Article Synopsis

  • Radiation therapy is commonly used to treat hepatocellular carcinoma (HCC), but its effectiveness can be reduced by the over-expression of PD-L1, which promotes resistance to treatment.
  • This study explores the potential of nifuroxazide to enhance radiotherapy's effectiveness by lowering PD-L1 levels, demonstrating that it increases tumor cell sensitivity to radiation while promoting cell death (apoptosis).
  • Nifuroxazide not only inhibited tumor growth and improved survival rates in H22-bearing mice, but also helped decrease PD-L1 expression in tumor tissues, suggesting it may be a valuable adjunct to radiation therapy for HCC patients.

Article Abstract

Radiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression. Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosis in vitro. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10942647PMC
http://dx.doi.org/10.7554/eLife.90911DOI Listing

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