TY - JOUR
T1 - Antitumor effect of lenalidomide in malignant glioma cell lines
AU - Hanashima, Yuya
AU - Sano, Emiko
AU - Sumi, Koichiro
AU - Ozawa, Yoshinari
AU - Yagi, Chihiro
AU - Tatsuoka, Juri
AU - Yoshimura, Sodai
AU - Yamamuro, Shun
AU - Ueda, Takuya
AU - Nakayama, Tomohiro
AU - Hara, Hiroyuki
AU - Yoshino, Atsuo
N1 - Funding Information:
This research study was supported in part by a grant from the Health Sciences Research Institute, Inc. (Yokohama, Japan) for the Division of Companion Diagnostics, Department of Pathology and Microbiology, Nihon University School of Medicine (Tokyo, Japan).
Publisher Copyright:
© 2020 Spandidos Publications. All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell cycle arrest
KW - Drug repositioning
KW - Lenalidomide
KW - Malignant glioma
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U2 - 10.3892/or.2020.7543
DO - 10.3892/or.2020.7543
M3 - Article
C2 - 32323826
AN - SCOPUS:85081699856
SN - 1021-335X
VL - 43
SP - 1580
EP - 1590
JO - Oncology Reports
JF - Oncology Reports
IS - 5
ER -