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DOI: 10.1055/s-0042-1748714
Mebendazole inhibits growth of hepatoblastoma cells by cell cycle arrest
Although survival of hepatoblastoma patients has dramatically increased by combining preoperative chemotherapy and surgical tumor resection, drug resistance remains a huge challenge in the clinical management. Here, we integrated gene expression data of five responders and two non-responders into the pharmacologic perturbation prediction tool Connectivity Map and identified the anthelmintic mebendazole as a putative drug to circumvent chemoresistance in hepatoblastoma. Mebendazole treatment of cell lines grown from patient-derived xenografts resulted in a potent reduction of tumor cell growth in a dose-dependent manner. Moreover, mebendazole treatment resulted in a reduced colony formation capability, induction of apoptosis, and cell cycle arrest in G2/M phase, which was associated with blockage of microtubule formation. Consequently, RNA sequencing analyses confirmed the transcriptional downregulation of tubulins. Using a subcutaneous patient-derived xenograft transplantation model we found that mebendazole significantly reduced tumor growth in vivo. In conclusion, our results strongly support the clinical use of mebendazole in the treatment of chemoresistant hepatoblastoma.
Publication History
Article published online:
17 May 2022
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