Behruzi M, Ghorbanlou M, Shabani R, Rustamzadeh A, Alhagh Gorgich E, Seidkhani E, et al . Vismodegib Improved Therapy of Medulloblastoma by Targeting Sonic Hedgehog Signaling Pathway on DAOY Medulloblastoma Cell Line. BCN 2025; 16 (3) :609-618
URL:
http://bcn.iums.ac.ir/article-1-2905-en.html
1- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
2- Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran. & Department of Anatomical Sciences, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
3- Department of Anatomy, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran.
4- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. & Reproductive Sciences and Technology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Abstract:
Introduction: Targeting smoothened (SMO) has been a remarkable strategy for treating sonic hedgehog (Shh)-dependent cancers, especially medulloblastoma. GDC-0449, also known as vismodegib, is a potent SMO inhibitor with mild toxicity and high affinity. Thus, this study aimed to investigate the anti-medulloblastoma efficacy of vismodegib in the DAOY medulloblastoma cell line.
Methods: Human DAOY medulloblastoma cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM). 50, 80, 100, and 150 μM doses of vismodegib were used to treat cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), scratch, and trypan blue assays, as well as real-time polymerase chain reaction (RT-PCR) and immunofluorescence studies, were performed 24 and 48 h post-treatment.
Results: The MTT and trypan blue assays showed a significant difference in viability between the control and treatment groups. The results of the scratch assay showed that in the control group, the cells were able to repair the lesion, while the scratch disintegrated at higher doses of vismodegib. The expression of SMO, Gli1, and MYCN genes, the main components of the SHH signalling pathway, was significantly reduced in the vismodegib-treated groups compared to the control group. Also, a notable increase in the activation of metastasis-promoting genes (Bax and p53) and a reduction in the activation of the metastasis-inhibiting gene (Bcl2) were observed.
Conclusion: The results of the current study confirm that vismodegib is a potent inhibitor of the Shh pathway and may be used in combination with new therapeutic methods to treat medulloblastoma.
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● Vismodegib is a potent inhibitor of SMO in the DAOY medulloblastoma cell line.
● Vismodegib can regulate cell viability and apoptosis in Shh-dependent cancer cells.
● Vismodegib could be considered as adjunct therapy for Shh medulloblastoma.
Plain Language Summary
Vismodegib is a medication that targets a signaling pathway known as the Sonic Hedgehog (Shh) pathway. This pathway plays an important role in cell growth and development. In this study, we aimed to find out if vismodegib can affect a type of brain cancer, called medulloblastoma. We used human DAOY medulloblastoma cells line in the lab. The cells were treated with different doses of vismodegib. Then, we performed various tests to see the effects of the drug on the cells. Vismodegib reduced the viability of DAOY cells significantly. The scratch assay results showed that the cells that did not receive Vismodegib were able to repair the wound, but in those received higher doses of Vismodegib, the scratch was not repaired properly. This finding shows that the drug inhibits cell migration and regeneration. Vismodegib managed to reduce the expression of SMO, Gli1, and MYCN. These genes are crucial for Shh-cancer cell growth. It also increased the activation of Bax and p53 genes which promote cancer, while reduced Bcl2 gene, which inhibits cancer. This study confirms that vismodegib is a potent inhibitor of the Shh signaling pathway and it can be used as a promising treatment for Shh medulloblastoma.
Type of Study:
Original |
Subject:
Cellular and molecular Neuroscience Received: 2024/03/17 | Accepted: 2024/04/11 | Published: 2025/05/29