Related Experiment Video
Updated: Dec 14, 2025
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
Combination Therapy with Nanomicellar-Curcumin and Temozolomide for In Vitro Therapy of Glioblastoma Multiforme via
Ali Bagherian1, Rajab Mardani2, Bostan Roudi1
1Department of Biology, Faculty of Science, Islamic Azad University, Damghan Branch, Damghan, Iran.
Abstract:
Glioblastoma (GBM) is the most serious brain tumor and shows a high rate of drug resistance. Wnt signaling is a very important pathway in GBM that can activate/inhibit other pathways, such as apoptosis and autophagy. In this study, we evaluated the efficacy of a combination of temozolomide (TMZ) plus curcumin or nanomicellar-curcumin on the inhibition of GBM growth in vitro, via effects on autophagy, apoptosis, and the Wnt signaling pathway. Two concentrations of curcumin and nanomicellar-curcumin (i.e., 20 μM and 50 μM) alone, and in combination with TMZ (50 μM) were used to induce cytotoxicity in the U87 GBM cell line. Wnt signaling-, autophagy-, and apoptosis-related genes were assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blots. All treatments (except 20 μM curcumin alone) significantly decreased the viability of U87 cells compared to controls. Curcumin (50 μM), nanomicellar-curcumin alone and in combination with TMZ significantly decreased the invasion and migration of U87 cells. Autophagy-related proteins (Beclin 1, LC3-I, LC3-II) were significantly increased. Apoptosis-related proteins (Bcl-2 and caspase 8) were also significantly increased, while Bax protein was significantly decreased. The expression levels of Wnt pathway-associated genes (β-catenin, cyclin D1, Twist, and ZEB1) were significantly reduced.
Insights
Curcumin and nanomicellar-curcumin, combined with temozolomide, effectively inhibit glioblastoma growth by modulating autophagy, apoptosis, and Wnt signaling pathways in vitro.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with significant drug resistance.
- The Wnt signaling pathway plays a crucial role in GBM, influencing apoptosis and autophagy.
- Targeting these pathways offers potential therapeutic strategies for GBM.
Purpose of the Study:
- To evaluate the efficacy of temozolomide (TMZ) combined with curcumin or nanomicellar-curcumin in inhibiting GBM growth.
- To investigate the effects of these combinations on autophagy, apoptosis, and Wnt signaling in GBM cells.
- To assess the impact on GBM cell viability, invasion, and migration.
Main Methods:
- U87 GBM cells were treated with varying concentrations of curcumin, nanomicellar-curcumin, and TMZ.
- Cytotoxicity, invasion, and migration were assessed.
- Gene and protein expression related to Wnt signaling, autophagy, and apoptosis were analyzed using qRT-PCR and Western blots.
Main Results:
- Most treatments significantly reduced U87 cell viability, invasion, and migration.
- Curcumin and nanomicellar-curcumin, alone and with TMZ, showed significant effects.
- Key proteins involved in autophagy (Beclin 1, LC3) and apoptosis (Bcl-2, caspase 8) were upregulated, while Bax was downregulated.
- Wnt pathway genes (β-catenin, cyclin D1, Twist, ZEB1) were significantly downregulated.
Conclusions:
- Combination therapy with temozolomide, curcumin, and nanomicellar-curcumin demonstrates significant anti-glioblastoma effects in vitro.
- These agents modulate critical pathways including Wnt signaling, autophagy, and apoptosis.
- Nanomicellar-curcumin shows promise as a drug delivery system to enhance GBM treatment efficacy.
