Resveratrol restores sensitivity of glioma cells to temozolamide through inhibiting the activation of Wnt signaling pathway
Journal of Cellular Physiology
Published online on October 14, 2018
Abstract
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- "\nAbstract\nMalignant gliomas are aggressive primary neoplasms that originate in
the glial cells of the brain or the spine with notable resistance to standard treatment
options. We carried out the study with the aim to shed light on the sensitization
of resveratrol to temozolomide (TMZ) against glioma through the Wnt signaling pathway.
Initially, glioma cell lines with strong resistance to TMZ were selected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium
bromide (MTT) assay. Then, the glioma cells were subjected to resveratrol, TMZ,
Wnt signaling pathway inhibitors, and activators. Cell survival rate and inhibitory
concentration at half maximum value were detected by MTT, apoptosis by flow cytometry,
and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining,
in vitro proliferation by hanging drop method and β‐catenin translocation into nuclei
by TOP/FOP‐FLASH assay. The expressions of the Wnt signaling pathway‐related and
apoptosis‐related factors were determined by western blot analysis. Nude mice with
glioma xenograft were established to detect tumorigenic ability. Glioma cell lines
T98G and U138 which were highly resistant to TMZ were selected for subsequent experiments.
Resveratrol increased the efficacy of TMZ by restraining cell proliferation, tumor
growth, and promoting cell apoptosis in glioma cells. Resveratrol inhibited Wnt2
and β‐catenin expressions yet elevated GSK‐3β expression. Moreover, the Wnt signaling
pathway participates in the sensitivity enhancing of resveratrol to TMZ via regulating
\nO\n6‐methylguanine‐DNA methyltransferase (MGMT) expression. Resveratrol sensitized
TMZ‐induced glioma cell apoptosis by repressing the activation of the Wnt signaling
pathway and downregulating MGMT expression, which may confer new thoughts to the
chemotherapy of glioma."
- Journal of Cellular Physiology, EarlyView.