Takeda Hiroyuki, Okada Masashi, Kuramoto Kenta, Suzuki Shuhei, Sakaki Hirotsugu, Sanomachi Tomomi, Seino Shizuka, Yoshioka Takashi, Hirano Hirofumi, Arita Kazunori, Kitanaka Chifumi
Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
Oncotarget. 2017 Jun 29;8(53):90996-91008. doi: 10.18632/oncotarget.18827. eCollection 2017 Oct 31.
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. , gemcitabine inhibited the growth of high-grade meningioma cells effectively by inducing S-phase arrest and apoptotic cell death. , 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 . 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.
目前,对于手术后复发且接受过放疗的高级别脑膜瘤,尚无既定的治疗方案,且很少有化疗药物正在研发用于治疗高级别脑膜瘤。在本研究中,我们筛选了一组化疗药物,以研究它们在高级别脑膜瘤中可能的抗肿瘤活性,发现高级别脑膜瘤细胞对抗代谢物具有优先敏感性,特别是对吉西他滨。吉西他滨通过诱导S期阻滞和凋亡性细胞死亡,有效抑制了高级别脑膜瘤细胞的生长。全身应用吉西他滨化疗不仅抑制了肿瘤起始,还抑制了高级别脑膜瘤异种移植模型中已形成肿瘤的生长并实现了长期控制。组织学分析表明,全身应用吉西他滨可阻断肿瘤细胞的细胞周期进程并促进凋亡性细胞死亡。总之,我们的数据表明吉西他滨通过细胞周期阻滞和细胞毒性机制对高级别脑膜瘤发挥强大的抗肿瘤活性。因此,我们认为吉西他滨是一种有前景的化疗药物,值得作为高级别脑膜瘤的治疗选择进行进一步研究。