Evidence mapPaperPMID 41225557Full record

ArticleCancer cell international2025

The effect of combination therapy on Bevacizumab, Carmustine, and Metformin chemotherapy drugs on the fluctuating performance expression of TLR2, TLR6, and IL-6 genes in the cell line of brain glioblastoma.

Seyedeh Elham Norollahi, Bahman Yousefi, Shahrokh Yousefzadeh-Chabok, Fatemeh Nejatifar, Mohammad Samadian, Mehdi Evazalipour, Mohamad Eftekhary, Masoud Faghih Akhlaghi, Ebrahim Mirzajani, Ali Rashidy-Pour and 1 more

Abstract read
In one paragraph

Article in Cancer cell international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Seyedeh Elham NorollahiCancer Research Center, Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
Bahman YousefiCancer Research Center, Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
Shahrokh Yousefzadeh-ChabokGuilan Road Trauma Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran.
Fatemeh NejatifarDepartment of Hematology and Oncology, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran.
Mohammad SamadianDepartment of Neurosurgery, School of Medicine, Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mehdi EvazalipourDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.
Mohamad EftekharyDepartment of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran.
Masoud Faghih AkhlaghiDepartment of Medicinal Chemistry, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.
Ebrahim MirzajaniDepartment of Biochemistry and Biophysics, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Ali Rashidy-PourResearch Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran. Arashidy_pour44@yahoo.com.
Ali Akbar SamadaniGuilan Road Trauma Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran. a.a.hormoz@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveGlioblastoma, one of the most aggressive brain tumors, is distinguished by its resistance to standard treatments. So, studying practical therapeutic methods is of great importance. In this project, the effects of combined chemotherapy drugs, including bevacizumab, carmustine, and metformin, on the expression of IL-6, TLR2, and TLR6 in the glioblastoma cell line of U87MG were investigated.

methodsU87MG cells were treated with bevacizumab, carmustine, and metformin alone or in combined groups. Cell viability was measured using the MTT assay. Apoptotic rates and cell cycle were analyzed by flow cytometry. Gene and protein expression levels of TLR2, TLR6, and IL-6 were evaluated by Real-Time PCR and Western blotting, respectively. In addition, bioinformatic analyses, including protein-protein interaction (PPI) network construction and pathway enrichment, were performed using Cytoscape (GeneMANIA) and R (ClusterProfiler).

resultsThe triple-drug combination(bevacizumab, carmustine, and metformin )significantly reduced cell viability and induced a substantial increase in apoptosis and G0/G1 cell cycle arrest. Treatment also led to a marked downregulation of TLR2, TLR6, and IL-6 gene expression. Bioinformatic analysis revealed these genes to be central in pathways associated with immune regulation, inflammation, and tumor progression.

conclusionThe combination of bevacizumab, carmustine, and metformin exerts a potent synergistic antitumor effect in U87MG glioblastoma cells through modulation of inflammation-associated genes, induction of apoptosis, and disruption of cell cycle progression. These findings provide a mechanistic rationale for multi-targeted combination therapy in glioblastoma and support further preclinical evaluation.

Indexed as

Chemotherapy drugsCombination therapyGlioblastomaTLR signaling

Identifiers

PMID41225557
PMCPMC12613698

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.