Validation of Enhancing Effects of Curcumin on Radiotherapy with F98/ FGT Glioblastoma-Bearing Rat Model

Int J Mol Sci. 2020 Jun 19;21(12):4385. doi: 10.3390/ijms21124385.

Abstract

Glioblastoma, the most common and aggressive brain tumor with low survival rate, is difficult to be cured by neurosurgery or radiotherapy. Mounting evidence has reported the anti-inflammatory and anticancer effects of curcumin on several types of cancer in preclinical studies and clinical trials. To our knowledge, there is no platform or system that could be used to effectively and real-timely evaluate the therapeutic efficacy of curcumin for glioblastoma multiforme (GBM). In this study, we constructed a lentivirus vector with triple-reporter genes (Fluc/GFP/tk) and transduced into rat F98 glioblastoma cells to establish an orthotopic F98/FGT glioma-bearing rat model. In the model, the therapeutic efficacies for curcumin alone, radiation alone, and their combination were evaluated via noninvasive bioluminescent imaging and overall survival measurements. At the cell level, curcumin is capable of causing a G2/M cell cycle arrest and sensitizing the F98 cells to radiation. In animal model, curcumin synergistically enhances the effects of radiotherapy on suppressing the growth of both transplanted glioma cells and in situ brain tumors, and extending the overall survival periods longer than those of curcumin alone and radiation alone treatments. In conclusion, we have demonstrated that curcumin may serve as a novel radiosensitizer to combine with radiotherapy using the triple-reporter F98/FGT animal model for effective and simultaneous evaluation of therapeutic efficacy.

Keywords: F98/FGT; curcumin; glioblastoma; radiosensitizer.

MeSH terms

  • Animals
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / genetics
  • Brain Neoplasms / therapy*
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chemoradiotherapy
  • Curcumin / administration & dosage*
  • Curcumin / pharmacology
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / genetics
  • Glioblastoma / therapy*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lentivirus / genetics*
  • Luciferases / genetics
  • Luciferases / metabolism
  • Magnetic Resonance Imaging
  • Radiation-Sensitizing Agents / administration & dosage*
  • Radiation-Sensitizing Agents / pharmacology
  • Rats
  • Rats, Transgenic
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Radiation-Sensitizing Agents
  • Green Fluorescent Proteins
  • Luciferases
  • Thymidine Kinase
  • Curcumin