Resveratrol Enhances the Radiosensitivity by Inducing DNA Damage and Antitumor Immunity in a Glioblastoma Rat Model under 3 T MRI Monitoring

Abstract

Glioblastoma (GBM) is the most common intracranial tumor with characteristic of malignancy. Resveratrol, a natural originated polyphenolic compound, has been reported to act as a potential radiosensitizer in cancer therapy. Magnetic resonance imaging (MRI) is the first choice for the diagnosis, pathological grading, and efficacy evaluation of GBM. In this study, MRI was applied to observe whether resveratrol could intensify the anti-GBM tumor effect by enhancing antitumor immunity during radiotherapy. We established an intracranial C6 GBM model in SD rats, treated with radiation and resveratrol. The increased body weight, the inhibition on mortality, and tumor volume in radiated- GBM rats were further enhanced by resveratrol addition, while the pathological damage of brain was alleviated. The modulation of radiation on inflammation, cell cycle, and apoptosis was strengthened by resveratrol; and Ki-67, PD-L1, and cell cycle- and apoptosis-related protein expressions were also improved by cotreatment. Besides, cotreatment attenuated DNA damage and induced G0/G1-phase cell arrest of GBM rats, accompanied with the changed expression of ATM-AKT-STAT3 pathway-related proteins. Moreover, the percentages of CD3+CD8+T cells and IFN-γ+CD8+T cells were enhanced, while (CD4+CD25+Foxp3)/CD4+T cells were decreased by radiation or resveratrol, which was strengthened by cotreatment. The modulation effect of cotreatment on CD3, Foxp3, and IFN-γ levels was also stronger than radiation or resveratrol alone. To conclude, resveratrol enhanced the effect of radiotherapy by inducing DNA damage and antitumor immunity in the intracranial C6 GBM.

Roles of STAT3 in the pathogenesis and treatment of glioblastoma

“…For instance, resveratrol, a natural polyphenol with a stilbene structure derived from plants and fruits, has been shown to inhibit the proliferation and invasion of glioma cell in a STAT3-dependent manner. Resveratrol can penetrate the blood-brain barrier, and intrathecal injection allows high drug concentrations in vivo (Qian et al, 2022). Unexpectedly, it quickly metabolizes after systematical administration, resulting in very low bioavailability.…”

Sonodynamic therapy and Magnetic Resonance-guided Focused Ultrasound: new therapeutic strategy in Glioblastoma

“…Various new treatments have been proposed over the years, regarding use of CAR T cells [13], molecular agents enhancing the effect of Radiotherapy (RT) [14], up to the application of high and low intensity focus ultrasound [15].…”