Attenuated Salmonella carrying siRNA-CD24 improved the effect of oxaliplatin on HCC

Int Immunopharmacol. 2023 Nov;124(Pt B):111025. doi: 10.1016/j.intimp.2023.111025. Epub 2023 Oct 10.

Abstract

Oxaliplatin is a chemotherapy drug currently utilized in the treatment of advanced cancer patients. However, its tolerability poses a limitation to its clinical application. Studies have demonstrated that the presence of tumor-associated macrophages is positively correlated with poor prognosis in various solid tumors, including hepatocellular carcinoma (HCC), and is a significant factor contributing to oxaliplatin resistance. Therefore, targeting tumor-associated macrophages may be an effective strategy to improve the efficacy of oxaliplatin in the treatment of HCC patients. CD24 is a novel target for tumor therapy that can interact with the inhibitory receptor Siglec-10 on tumor-associated macrophages, transmitting immune inhibitory signals and inhibiting macrophage phagocytosis function. In this study, we utilized RNAi technology to inhibit the expression of CD24 in tumor cells and combined it with oxaliplatin, resulting in reduced tumor invasion, migration, and proliferation, as well as increased cell apoptosis. Furthermore, immunofluorescence and flow cytometry results indicated that both the single treatment group and combination treatment group enhanced the infiltration of immune cells. This study presents a novel approach to identifying combination therapy and targets for the clinical treatment of HCC with oxaliplatin.

Keywords: CD24; Hepatocellular; Oxaliplatin; RNAi; Salmonella.

MeSH terms

  • CD24 Antigen / genetics
  • CD24 Antigen / metabolism
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carrier Proteins
  • Cell Line, Tumor
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Oxaliplatin / pharmacology
  • Oxaliplatin / therapeutic use
  • RNA, Small Interfering / genetics

Substances

  • Oxaliplatin
  • RNA, Small Interfering
  • Carrier Proteins
  • CD24 protein, human
  • CD24 Antigen