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In vitro and in vivo efficacies of inhibitors of the EGFR/MEK/ERK signaling in the treatment of alveolar echinococcosis

Alveolar echinococcosis (AE), caused by the larval stage of the cestode Echinococcus multilocularis, is a lethal disease in humans. Novel therapeutic options are urgently needed as the current chemotherapy displays limited efficiency in AE treatment. In this study, we assessed the in vitro and in vivo effects of the EGFR/MEK/ERK signaling inhibitors including BIBW2992, CI-1033 and U0126 on E. multilocularis. Our data showed that BIBW2992, CI-1033 and U0126 all displayed in vitro effects on the viability of the E. multilocularis metacestode. They also showed protoscolecidal activities and caused severe ultrastructural alterations in the parasite. Moreover, BIBW2992 and CI-1033 exhibited potent proapoptotic effects on E. multilocularis metacestodes. Strikingly, a large portion of the apoptotic cells were found to be the germinative cells. In vivo studies showed that BIBW2992 and U0126 significantly reduced parasite burden, and the parasite obtained from BIBW2992-treated mice displayed impaired structural integrity of the germinal layer. In conclusion, these findings demonstrate the potential of EGFR-mediated signaling as a target for the development of novel anti-AE agents. The EGFR inhibitor BIBW2992 represents a promising drug candidate and/or a lead compound for anti-AE chemotherapy.

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