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

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.

Action of Curcumin on Glioblastoma Growth: A Systematic Review with Meta-Analysis of Animal Model Studies

“…However, the absence of observation of a significant effect might be due to the reduced number of studies, since only three studies were published and included in the metaanalysis that described the combined effect of curcumin plus radiation. In fact, in one study [31], combined treatment with curcumin plus radiation produced a significantly higher (p-value < 0.05) percentage of survival after 60 days of tumor implantation when compared with radiation alone, even though a significant reduction (p-value < 0.05) in tumor volume was not observed, probably because of the reduced number of animals (n = 2) used in the experiments evaluating tumor growth. Regarding the two other studies [37], a significant reduction (p-value < 0.05) in tumor volume was observed in mice treated with curcumin plus radiation when compared with radiation alone, but only for mice implanted with U251, not LN229 human glioblastoma cell lines, suggesting that the efficacy of combined curcumin plus radiation treatment might depend on the type of glioblastoma cell line.…”

“…Only one study by Meng et al, 2017 [37], did not disclose the number of tumor cells implanted in the animals (criterion 2) out of the twenty-four selected research studies, which are peer-reviewed publications (criterion 1). A further six studies [31,32,[38][39][40][41] did not address the randomization procedure for assigning tumor-bearing animals to treatment and control groups (criterion 3). Criteria 4 and 5-blinding the outcome evaluation and sample size calculation-were not mentioned in any of the included studies.…”

Pharmacotherapeutics and molecular docking studies of alpha-synuclein modulators as promising therapeutics for Parkinson’s disease

“…Curcumin is biologically most active and abundant among the three curcuminoids (Spinelli et al, 2015). Research has proven that this compound possesses antioxidant, anti-inflammatory, cardioprotective, neuroprotective (Wang et al, 2020), antiapoptotic (El Nebrisi et al, 2020, and chemopreventive (Scapagnini et al, 2011) properties. It also exhibits free radical scavenging activity, and such properties could combat nitrative and oxidative stress in various neurodegenerative disorders like PD and Alzheimer's disease.…”

Radiosensitization and Radioprotection by Curcumin in Glioblastoma and Other Cancers

“…The synergistic effects of curcumin and radiotherapy were also validated in an orthotopic F98/FGT glioma-bearing rat model. Curcumin enhanced the effects of radiotherapy resulting in increased suppression of the growth of in situ brain tumors and transplanted glioma cells alike [ 50 ].…”