2. Academic Validation
  3. Suppression of glioblastoma by a drug cocktail reprogramming tumor cells into neuronal like cells

Suppression of glioblastoma by a drug cocktail reprogramming tumor cells into neuronal like cells

  • Sci Rep. 2019 Mar 5;9(1):3462. doi: 10.1038/s41598-019-39852-5.
Longfei Gao 1,  Shichao Huang 2,  Hong Zhang 1 3,  Wei Hua 4,  Shunmei Xin 1,  Lin Cheng 5,  Wuqiang Guan 6,  Yongchun Yu 6,  Ying Mao 4 7,  Gang Pei 8 9 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China.
  • 2 Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
  • 3 School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210, China.
  • 4 Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
  • 5 State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 6 Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.
  • 7 State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, 131 Dong'an Road, Shanghai, 200032, China.
  • 8 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China. gpei@sibs.ac.cn.
  • 9 Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China. gpei@sibs.ac.cn.
  • 10 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China. gpei@sibs.ac.cn.
PMID: 30837577 DOI: 10.1038/s41598-019-39852-5
Abstract

Glioblastoma (GBM) is the most common and aggressive malignant tumor in adult brain. Even with the current standard therapy including surgical resection followed by postoperative radiotherapy and chemotherapy with temozolomide (Temo), GBM patients still have a poor median survival. Reprogramming of tumor cells into non-malignant cells might be a promising therapeutic strategy for malignant tumors, including GBM. Based on previous studies using small molecules to reprogram astrocytes into neuronal cells, here we further identified a FTT cocktail of three commonly used drugs (Fasudil, Tranilast, and Temo) to reprogram patient-derived GBM cells, either cultured in serum containing or serum-free medium, into neuronal like cells. FTT-treated GBM cells displayed a neuronal like morphology, expressed neuronal genes, exhibited neuronal electrophysiological properties, and showed attenuated malignancy. More importantly, FTT cocktail more significantly suppressed tumor growth and prolonged survival in GBM patient derived xenograft than Temo alone. Our study provided preclinical evidence that the neuronal reprogramming drug cocktail might be a promising strategy to improve the existing treatment for GBM.

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