Flubendazole presents anti-tumor effects by promoting cell cycle arrest and inhibiting the invadopodia in pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterised by its high aggressive biological tumor behavior leading to a poor prognosis. The existing chemotherapy regimes have considerable limitations such as drug resistance and serious adverse effects. Flubendazole is an antihelmintic drug with highly safety that is recently reported to be a potential anti-tumor agent in various types of human cancer cells. We conducted a series of assays to explore its role in PDAC, like CCK8 assays, transwell-migration and invasion assays. In addition, we constructed the invadopodia model in vitro to investigate the effect of flubendazole on invadopodia. We found that flubendazole could inhibit the viability of PDAC cells dose-dependently and time-dependently. It also caused G2/M arrest by disrupting the microtubule and also induce apoptosis. The migration of PDAC cells was attenuated and could be partly explained by the disruption of EMT caused by flubendazole. Besides, the invasion was weakened by flubendazole and the number of cells with mature invadopodia was also decreased. Moreover, it interfered the formation and maturation of invadopodia by inhibiting PI3K/Akt pathway and Src-mediated Tks5 phosphorylation, and thus inhibit the metastasis of PDAC cells. Due to its high safety, it may provide a novel insight for the prevention and treatment of pancreatic cancer metastasis.