Working Paper Article Version 1 This version is not peer-reviewed

Lomeguatrib Increases the Radiosensitivity of MGMT Unmethylated Human Glioblastoma Multiforme Cell Lines

Version 1 : Received: 2 June 2021 / Approved: 3 June 2021 / Online: 3 June 2021 (10:44:21 CEST)

A peer-reviewed article of this Preprint also exists.

Kirstein, A.; Schilling, D.; Combs, S.E.; Schmid, T.E. Lomeguatrib Increases the Radiosensitivity of MGMT Unmethylated Human Glioblastoma Multiforme Cell Lines. Int. J. Mol. Sci. 2021, 22, 6781. Kirstein, A.; Schilling, D.; Combs, S.E.; Schmid, T.E. Lomeguatrib Increases the Radiosensitivity of MGMT Unmethylated Human Glioblastoma Multiforme Cell Lines. Int. J. Mol. Sci. 2021, 22, 6781.

Journal reference: Int. J. Mol. Sci. 2021, 22, 6781
DOI: 10.3390/ijms22136781

Abstract

Background: Treatment resistance of glioblastoma multiforme to chemo- and radiotherapy remains a challenge yet to overcome. Especially MGMT promoter unmethylated patients have only little benefit from chemotherapy treatment using temozolomide since MGMT counteracts its therapeutic efficacy. Therefore, new treatment options in radiotherapy need to be developed to inhibit MGMT and increase radiotherapy response. Methods: Lomeguatrib, a highly specific MGMT inhibitor was used to inhibit MGMT protein expression in vitro. Radiosensitivity of established human glioblastoma multiforme cell lines in combination with lomeguatrib was investigated using the clonogenic survival assay. Inhibition of MGMT was analyzed using Western Blot. Cell cycle distribution and apoptosis were investigated to determine the effects of lomeguatrib alone as well as in combination with ionizing radiation. Results: Lomeguatrib significantly decreased MGMT protein expression and reduced radiation-induced G2/M arrest. A radiosensitizing effect of lomeguatrib was observed when administered at 1 µM and increased radioresistance at 20 µM. Conclusion: Low concentrations of lomeguatrib elicit radiosensitization, while high concentrations mediate a radioprotective effect.

Keywords

glioblastoma; MGMT; lomeguatrib; radiosensitivity; radiotherapy

Subject

BIOLOGY, Anatomy & Morphology

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