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Combined effects of niclosamide and temozolomide against human glioblastoma tumorspheres

Authors
 Hyeong-Cheol Oh  ;  Jin-Kyoung Shim  ;  Junseong Park  ;  Ji-Hyun Lee  ;  Ran Joo Choi  ;  Nam Hee Kim  ;  Hyun Sil Kim  ;  Ju Hyung Moon  ;  Eui Hyun Kim  ;  Jong Hee Chang  ;  Jong In Yook  ;  Seok-Gu Kang 
Citation
 JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, Vol.146(11) : 2817-2828, 2020-11 
Journal Title
 JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 
ISSN
 0171-5216 
Issue Date
2020-11
MeSH
Animals ; Antineoplastic Combined Chemotherapy Protocols / pharmacology* ; Brain Neoplasms / pathology* ; Cell Line, Tumor ; Cell Survival / drug effects ; Epithelial-Mesenchymal Transition / drug effects ; Glioblastoma / pathology* ; Humans ; Mice ; Neoplastic Stem Cells / drug effects ; Niclosamide / pharmacology ; Temozolomide / pharmacology ; Xenograft Model Antitumor Assays
Keywords
Glioblastoma ; Invasion ; Niclosamide ; Temozolomide ; Tumorsphere
Abstract
Purpose: Glioblastoma (GBM) is the most aggressive type of brain tumor and has poor survival outcomes, even after a combination of surgery, radiotherapy, and chemotherapy. Temozolomide is the only agent that has been shown to be effective against GBM, suggesting that combination of temozolomide with other agents may be more effective. Niclosamide, an FDA approved anthelmintic agent, has shown anti-cancer effects against human colon, breast, prostate cancers as well as GBM. However, the efficacy of the combination of niclosamide with temozolomide against GBM tumorspheres (TSs) has not been determined. We hypothesized that the combined treatment could effectively suppress GBM TSs. Methods: GBM TSs (TS15-88, GSC11) were treated with niclosamide and/or temozolomide. Combined effects of two drugs were evaluated by measuring viability, neurosphere formation, and 3D-invasion in collagen matrix. Transcriptional profiles of GBM TS were analyzed using RNA sequencing. In vivo anticancer efficacy of combined drugs was tested in a mouse orthotopic xenograft model. Results: Combination treatment of niclosamide and temozolomide significantly inhibited the cell viability, stemness, and invasive properties of GBM TSs. This combined treatment significantly down-regulated the expression of epithelial mesenchymal transition-related markers, Zeb1, N-cadherin, and β-catenin. The combined treatment also significantly decreased tumor growth in orthotopic xenograft models. Conclusion: The combination of niclosamide and temozolomide effectively decreased the stemness and invasive properties of GBM TSs, suggesting that this regimen may be therapeutically effective in treating patients with GBM.
Files in This Item:
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DOI
10.1007/s00432-020-03330-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Eui Hyun(김의현) ORCID logo https://orcid.org/0000-0002-2523-7122
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Moon, Ju Hyung(문주형)
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Chang, Jong Hee(장종희) ORCID logo https://orcid.org/0000-0003-1509-9800
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180163
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