Antitumor effect of lenalidomide in malignant glioma cell lines

Yuya Hanashima, Emiko Sano, Koichiro Sumi, Yoshinari Ozawa, Chihiro Yagi, Juri Tatsuoka, Sodai Yoshimura, Shun Yamamuro, Takuya Ueda, Tomohiro Nakayama, Hiroyuki Hara, Atsuo Yoshino

Research output: Contribution to journalArticle

Abstract

Glioblastoma is a malignant brain tumor exhibiting highly aggressive proliferation and invasion capacities. Despite treatment by aggressive surgical resection and adjuvant therapy including temozolomide and radiation therapy, patient prognosis remains poor. Lenalidomide, a derivative of thalidomide, is known to be an immunomodulatory agent that has been used to treat hematopoietic malignancies. There are numerous studies revealing an antitumor effect of lenalidomide in hematopoietic cells, but not in glioma cells. The present study aimed to demonstrate the antitumor effect of lenalidomide on malignant glioma cell lines. The growth inhibition of malignant glioma cells (A-172, AM-38, T98G, U-138MG, U-251MG, and YH-13) by lenalidomide was assessed using a Coulter counter. The mechanism of the antitumor effect of lenalidomide was examined employing a fluorescence–activated cell sorter, western blot analysis, and quantitative real-time reverse transcriptional polymerase chain reaction (RT-qPCR) in malignant glioma cell lines (A-172, AM-38). The results revealed that the number of malignant glioma cells was decreased in a concentration-dependent manner by lenalidomide. DNA flow cytometric analysis demonstrated an increase in the ratio of cells at the G0/G1 phase following lenalidomide treatment. Western blot analysis and RT-qPCR revealed that p53 activation and the expression of p21 were increased in glioma cells treated with lenalidomide. Western blot analysis revealed that cleavage of PARP did not occur; however, increased expression of Bax protein, cleavage of caspase–9 and cleavage of caspase–3 were confirmed. Analysis by FACS also supported the conclusion that little apoptosis induction occurred following lenalidomide treatment of malignant glioma cell lines. In conclusion, lenalidomide exerts an antitumor effect on glioma cells due to alterations in cell cycle distribution.

Original languageEnglish
Pages (from-to)1580-1590
Number of pages11
JournalOncology Reports
Volume43
Issue number5
DOIs
Publication statusPublished - 2020

Keywords

  • Apoptosis
  • Cell cycle arrest
  • Drug repositioning
  • Lenalidomide
  • Malignant glioma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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