Ultrastructural and immunohistochemical insights on the anti-glioma effects of a dual-drug cocktail in an in vivo experimental model

J Chemother. 2024 Nov;36(7):593-606. doi: 10.1080/1120009X.2024.2302741. Epub 2024 Jan 19.

Abstract

Glioma coined as 'butterfly tumor' exhibits intense heterogeneity at the molecular and cellular levels. Although, Temozolomide exerted a long-ranging and prevailing therapeutic effect against glioma, albeit it has provided modest survival outcome. Fucoidan, (marine brown algal derivative) has demonstrated potent anti-tumor effects including glioma. Nevertheless, there is paucity of studies conducted on Fucoidan to enhance the anti-glioma efficacy of Temozolomide. The present study aimed to explore the plausible synergistic anti-glioma efficacy of Fucoidan in combination with Temozolomide in an in vivo experimental model. The dual-drug combination significantly inhibited tumor growth in in vivo and prolonged the survival rate when compared with the other treatment and tumor-control groups, via down-regulation of inflammatory cascade- IL-6/T LR4 and JAK/STAT3 as per the immunohistochemistry findings. Furthermore, the ultrastructural analysis indicated that the combinatorial treatment had restored the normal neuronal architecture of glioma-induced rats. Overall, the dual-drug cocktail might enhance the therapeutic outcome in glioma patients.

Keywords: Glioma; fucoidan; immunohistochemistry; inflammation; temozolomide; ultrastructural.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / secondary
  • Disease Models, Animal
  • Drug Synergism
  • Glioma* / drug therapy
  • Glioma* / pathology
  • Immunohistochemistry
  • Interleukin-6 / metabolism
  • Male
  • Polysaccharides* / pharmacology
  • Rats
  • STAT3 Transcription Factor / metabolism
  • Temozolomide* / pharmacology
  • Temozolomide* / therapeutic use

Substances

  • Temozolomide
  • Polysaccharides
  • fucoidan
  • STAT3 Transcription Factor
  • Interleukin-6