Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Germany.
Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Germany.
Radiother Oncol. 2015 Sep;116(3):381-7. doi: 10.1016/j.radonc.2015.08.007. Epub 2015 Aug 29.
In malignant glioma the presence of the IDH1 mutation (IDH1(R132H)) is associated with better clinical outcome. However, it is unclear whether IDH1 mutation is associated with a less aggressive phenotype or directly linked to increased sensitivity to radiotherapy.
We determined the influence of IDH1(R132H) mutant protein on proliferation and growth in 3D culture, migration, cell survival and radiosensitivity in vitro under normoxia (21% O2) and hypoxia (<1% O2) in a panel of human malignant glioma cell lines (U-251MG, U-343MG, LN-229) with stable overexpression of wild-type (IDH1(wt)) and mutated IDH1 (IDH1(R132H)).
Overexpression of IDH1(R132H) in glioma cells resulted in slightly decreased cell proliferation, considerably reduced cell migration and caused differences in growth properties in 3D spheroid cultures. Furthermore, IDH1(R132H)-positive cells consistently demonstrated an increased radiosensitivity in human malignant glioma cells U-251MG (DMF10: 1.52, p<0.01 and 1.42, p<0.01), U-343MG (DMF10: 1.78, p<0.01 and 1.75, p<0.01) and LN-229 (DMF10: 1.41, p<0.05 and 1.68, p<0.01) under normoxia and hypoxia, respectively.
Our data indicate that IDH1(R132H) mutation causes both a less aggressive biological behavior and direct radiosensitization of human malignant glioma cells. Targeting IDH1 appears to be an attractive approach in combination with radiotherapy.
在恶性胶质瘤中，存在 IDH1 突变（IDH1[R132H]）与更好的临床结果相关。然而，目前尚不清楚 IDH1 突变是否与侵袭性行为减少有关，或者是否与对放疗的敏感性增加直接相关。
我们在一组人恶性神经胶质瘤细胞系（U-251MG、U-343MG、LN-229）中，通过稳定过表达野生型（IDH1[wt]）和突变型 IDH1（IDH1[R132H]），确定 IDH1[R132H]突变蛋白在 3D 培养中的增殖和生长、迁移、细胞存活和放疗敏感性的影响，在常氧（21% O2）和缺氧（<1% O2）条件下进行体外研究。
胶质瘤细胞中 IDH1[R132H]的过表达导致细胞增殖略有下降，细胞迁移明显减少，并导致 3D 球体培养中的生长特性差异。此外，IDH1[R132H]阳性细胞在人恶性神经胶质瘤细胞 U-251MG（DMF10：1.52，p<0.01 和 1.42，p<0.01）、U-343MG（DMF10：1.78，p<0.01 和 1.75，p<0.01）和 LN-229（DMF10：1.41，p<0.05 和 1.68，p<0.01）中，常氧和缺氧条件下，分别表现出更高的放疗敏感性。
我们的数据表明，IDH1[R132H]突变导致人恶性神经胶质瘤细胞侵袭性行为减少和直接放疗增敏。针对 IDH1 似乎是一种有吸引力的方法，可与放疗联合应用。
