Oncotarget

Research Papers:

Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo

Hiroyuki Takeda, Masashi Okada, Kenta Kuramoto, Shuhei Suzuki, Hirotsugu Sakaki, Tomomi Sanomachi, Shizuka Seino, Takashi Yoshioka, Hirofumi Hirano, Kazunori Arita and Chifumi Kitanaka _

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Oncotarget. 2017; 8:90996-91008. https://doi.org/10.18632/oncotarget.18827

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Abstract

Hiroyuki Takeda1,2,*, Masashi Okada1,*, Kenta Kuramoto1, Shuhei Suzuki1,2, Hirotsugu Sakaki3, Tomomi Sanomachi1, Shizuka Seino1,4, Takashi Yoshioka2, Hirofumi Hirano5, Kazunori Arita5 and Chifumi Kitanaka1,4

1Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan

2Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan

3Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan

4Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan

5Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

*These authors contributed equally to this work

Correspondence to:

Chifumi Kitanaka, email: ckitanak@med.id.yamagata-u.ac.jp

Masashi Okada, email: m-okada@med.id.yamagata-u.ac.jp

Keywords: cancer, intracranial neoplasm, brain tumor, anaplastic meningioma, malignant meningioma

Received: April 07, 2017     Accepted: June 10, 2017     Published: June 29, 2017

ABSTRACT

Currently, there is no established therapeutic option for high-grade meningioma recurring after surgery and radiotherapy, and few chemotherapeutic agents are in development for the treatment of high-grade meningioma. Here in this study, we screened a panel of chemotherapeutic agents for their possible antitumor activity in high-grade meningioma and discovered that high-grade meningioma cells show a preferential sensitivity to antimetabolites, in particular, to gemcitabine. In vitro, gemcitabine inhibited the growth of high-grade meningioma cells effectively by inducing S-phase arrest and apoptotic cell death. In vivo, systemic gemcitabine chemotherapy suppressed not only tumor initiation but also inhibited the growth and achieved a long-term control of established tumors in xenograft models of high-grade meningioma. Histological analysis indicated that systemic gemcitabine blocks cell cycle progression and promotes apoptotic cell death in tumor cells in vivo. Together, our data demonstrate that gemcitabine exerts potent antitumor activity against high-grade meningioma through cytostatic and cytotoxic mechanisms. We therefore propose gemcitabine is a promising chemotherapeutic agent that warrants further investigation as a treatment option for high-grade meningioma.


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