A multi‑targeted tyrosine kinase inhibitor lenvatinib for the treatment of mice with advanced glioblastoma

  • Authors:
    • Jia Li
    • Chang‑Lin Zou
    • Zhi‑Ming Zhang
    • Lian‑Jie Lv
    • Hai‑Bo Qiao
    • Xiu‑Ju Chen
  • View Affiliations

  • Published online on: September 11, 2017     https://doi.org/10.3892/mmr.2017.7456
  • Pages: 7105-7111
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Glioblastoma is the most aggressive primary brain tumor that originates from the glial cells in adults. Aberrant angiogenesis is essential for malignant glioblastoma tumorigenesis, development and metastasis. Lenvatinib is a multi‑targeted anticancer agent that targets of receptor tyrosine kinases including vascular endothelial growth factor receptor 1 and 2, fibroblast growth factor receptor 1, platelet‑derived growth factor receptor β and v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog. In the present study, the therapeutic effects of lenvatinib as a treatment for glioblastoma were investigated in vivo and in vitro. The maximum dose toxicity (MDT) and treatment‑associated adverse events of lenvatinib were identified by cytotoxicity assay in experimental mice. Increasing levels of the pro‑apoptosis genes caspase‑3, -8, -9 and -10 following lenvatinib treatment were determined by reverse transcription‑quantitative polymerase chain reaction, and apoptosis of the malignant gliomas cells was analyzed by FACS. In vivo treatment with lenvatinib for BV‑2 bearing male BALC/c nude mice was assessed via tumor growth suppression and long‑term observation of survival. Subsequent cytotoxic T lymphocyte responses were further analyzed to determine the in vivo efficacy of lenvatinib treatment in mice with glioblastoma. The MDT of lenvatinib was identified as 0.24 mg, with relatively few side effects and improved efficacy in mice. Lenvatinib (0.24 mg) significantly increased apoptosis in BV‑2, C6, BC3H1 and G422 glioma cell lines. Tumor growth was significantly inhibited and tumor‑bearing mice demonstrated an improved survival rate following treatment with lenvatinib. In conclusion, lenvatinib provided an effective treatment outcome, and the results of the present study may help to achieve a comprehensive therapeutic schedule for clinical application.
View Figures
View References

Related Articles

Journal Cover

November-2017
Volume 16 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Zou CL, Zhang ZM, Lv LJ, Qiao HB and Chen XJ: A multi‑targeted tyrosine kinase inhibitor lenvatinib for the treatment of mice with advanced glioblastoma. Mol Med Rep 16: 7105-7111, 2017
APA
Li, J., Zou, C., Zhang, Z., Lv, L., Qiao, H., & Chen, X. (2017). A multi‑targeted tyrosine kinase inhibitor lenvatinib for the treatment of mice with advanced glioblastoma. Molecular Medicine Reports, 16, 7105-7111. https://doi.org/10.3892/mmr.2017.7456
MLA
Li, J., Zou, C., Zhang, Z., Lv, L., Qiao, H., Chen, X."A multi‑targeted tyrosine kinase inhibitor lenvatinib for the treatment of mice with advanced glioblastoma". Molecular Medicine Reports 16.5 (2017): 7105-7111.
Chicago
Li, J., Zou, C., Zhang, Z., Lv, L., Qiao, H., Chen, X."A multi‑targeted tyrosine kinase inhibitor lenvatinib for the treatment of mice with advanced glioblastoma". Molecular Medicine Reports 16, no. 5 (2017): 7105-7111. https://doi.org/10.3892/mmr.2017.7456