Response of medulloblastoma cells to vincristine and lomustine: Role of TRKC, CTNNB1 and STK15

Zakia Shinwari, Hindi Al, Essam Al-Shail, Yasser Khafaga, Amani Al-Kofide, Naser Elkum, Abdelilah Aboussekhra

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5 Citations (Scopus)

Abstract

Background: Vincristine and lomustine are two important chemotherapeutic drugs used for the treatment of different types of neoplasms, including medulloblastomas. Materials and Methods: We investigated the effects of vincristine and lomustine on 12 primary medulloblastoma cell cultures and the DAOY cell line using the annexin V-flow cytometry and immunoblotting techniques, following treatment of cells for different periods of time. Results: Both drugs triggered apoptosis and cell cycle delay at the G2/M phase and also up-regulated p16. Furthermore, the expression of 8 different cancer-related genes were assessed and their mRNA and protein levels were found to be highly heterogeneous and did not correlate in several medulloblastoma cultures. Importantly, there was significant correlation between the level of cadherin-associated protein beta 1 (CTNNB1) and Aurora kinase A (STKI5) proteins and neurotrophic tyrosine kinase receptor type 3 (TRKC) mRNA and the proportion of apoptosis induced by vincristine, the combination of both drugs, and lomustine, respectively. Conclusion: These genes could be of great importance as therapeutic biomarkers during the treatment of medulloblastoma patients with vincristine and lomustine.

Original languageEnglish
Pages (from-to)1721-1733
Number of pages13
JournalAnticancer Research
Volume31
Issue number5
Publication statusPublished - May 2011
Externally publishedYes

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Keywords

  • Apoptosis
  • Chemotherapy
  • Lomustine
  • Medulloblastoma
  • Vincristine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Shinwari, Z., Al, H., Al-Shail, E., Khafaga, Y., Al-Kofide, A., Elkum, N., & Aboussekhra, A. (2011). Response of medulloblastoma cells to vincristine and lomustine: Role of TRKC, CTNNB1 and STK15. Anticancer Research, 31(5), 1721-1733.