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

作者：Takeda Hiroyuki; Okada Masashi^*; Kuramoto Kenta; Suzuki Shuhei; Sakaki Hirotsugu; Sanomachi Tomomi; Seino Shizuka; Yoshioka Takashi; Hirano Hirofumi; Arita Kazunori; Kitanaka Chifumi^*

来源：Oncotarget, 2017, 8(53): 90979-90991.

DOI：10.18632/oncotarget.18827

• cancer
• intracranial neoplasm
• brain tumor
• anaplastic meningioma
• malignant meningioma

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.

• 出版日期2017-10-31