Terzis A J, Pedersen P H, Feuerstein B G, Arnold H, Bjerkvig R, Deen D F
Department of Neurosurgery, Luebeck, Germany.
J Neurooncol. 1998 Jan;36(2):113-21. doi: 10.1023/a:1005811403041.
The polyamine inhibitor DL-alpha-difluoromethylornithine (DFMO) is a specific irreversible inhibitor of ornithine decarboxylase which is a rate-limiting enzyme in the polyamine bio-synthesis pathway. The present study describes the effects of DFMO on glioma cell proliferation, migration and invasion using multicellular spheroids from three glioma cell lines (GaMg, U-251 Mg and U-87 Mg). 10 mM DFMO reduced cell migration in the three cell lines by about 30-50%. 1 mM putrescine, added together with DFMO inhibited the DFMO effect. A stronger effect was observed in the growth assay where 10 mM DFMO reduced the spheroid growth, for all cell lines, by 90%. This effect was also reversed by adding 1 mM of putrescine. In vitro tumor cell invasion experiments indicated after 3 days of confrontation, an extensive invasion also after 10 mM DFMO treatment. The brain aggregate volumes were reduced to about the same extent as in the absence of drug, suggesting essentially no effects of DFMO on the invasive process. It is concluded that the tumor spheroids retained their ability to invade normal brain tissue even after DFMO exposure. However, DFMO inhibited spheroid growth and cell migration which supports the notion that cell growth, migration and invasion are biological properties that are not necessarily related to each other.
多胺抑制剂DL-α-二氟甲基鸟氨酸（DFMO）是鸟氨酸脱羧酶的一种特异性不可逆抑制剂，鸟氨酸脱羧酶是多胺生物合成途径中的限速酶。本研究使用来自三种胶质瘤细胞系（GaMg、U-251 Mg和U-87 Mg）的多细胞球体，描述了DFMO对胶质瘤细胞增殖、迁移和侵袭的影响。10 mM DFMO使三种细胞系中的细胞迁移减少了约30%-50%。与DFMO一起添加的1 mM腐胺抑制了DFMO的作用。在生长试验中观察到更强的效果，其中10 mM DFMO使所有细胞系的球体生长减少了90%。添加1 mM腐胺也逆转了这种效果。体外肿瘤细胞侵袭实验表明，在对抗3天后，即使在10 mM DFMO处理后也有广泛的侵袭。脑聚集体体积减少到与未使用药物时大致相同的程度，这表明DFMO对侵袭过程基本没有影响。得出的结论是，即使在DFMO处理后，肿瘤球体仍保留其侵袭正常脑组织的能力。然而，DFMO抑制了球体生长和细胞迁移，这支持了细胞生长、迁移和侵袭是不一定相互关联的生物学特性这一观点。
