RT Journal Article SR Electronic T1 Thiabendazole inhibits glioblastoma cell proliferation and invasion targeting MCM2 JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP JPET-AR-2021-000852 DO 10.1124/jpet.121.000852 A1 Yaotian Hu A1 Wenjing Zhou A1 Zhiyi Xue A1 Xuemeng Liu A1 Zichao Feng A1 Yulin Zhang A1 Xun Zhang A1 Xiaofei Liu A1 Wenjie Li A1 Qing Zhang A1 Anjing Chen A1 Bin Huang A1 Jian Wang YR 2021 UL http://jpet.aspetjournals.org/content/early/2021/11/08/jpet.121.000852.abstract AB Thiabendazole (TBZ), approved by the U.S. Food and Drug Administration (FDA) for human oral use, elicits a potential anti-cancer activity on cancer cells in vitro and in animal models. Here, we evaluated the efficacy of TBZ in the treatment of human glioblastoma multiforme (GBM). TBZ reduced the viability of GBM cells (P3, U251, LN229, A172, and U118MG) relative to controls in a dose- and time-dependent manner. However, normal human astrocytes (NHA) exhibited a greater IC50 than tumor cells lines and were thus, more resistant to its cytotoxic effects. EdU positive cells and the number of colonies formed was decreased in TBZ-treated cells (at 150 μM, P < 0.05 and at 150 μM, P < 0.001, respectively). This decrease in proliferation was associated with a G2/M arrest as assessed with flow cytometry, and the downregulation of G2/M check point proteins. In addition, TBZ suppressed GBM cell invasion. Analysis of RNA sequencing data comparing TBZ treated cells with controls yielded a group of differentially expressed genes, the functions of which were associated with the cell cycle and DNA replication. The most significantly downregulated gene in TBZ-treated cells was mini-chromosome maintenance protein 2 (MCM2). SiRNA knockdown of MCM2 inhibited proliferation, causing a G2/M arrest in GBM cell lines and suppressed invasion. Taken together, our results demonstrated that TBZ inhibited proliferation and invasion in GBM cells through targeting of MCM2. Significance Statement TBZ inhibits the proliferation and invasion of glioblastoma cells by downregulating the expression of MCM2. These results support the repurposing of TBZ as a possible therapeutic drug in the treatment of GBM.