Antipsychotic Prochlorperazine Restrains Bladder Cancer Growth by Regulating cell proliferation and SRC-MEK-ERK Pathway

Abstract

Abstract The high incidence of bladder cancer and inconvenient life quality prompt us to find new therapeutic candidates. Prochlorperazine, mainly as an effective sedative, antiemetic reagent, was shown to exhibit anti-cancer activity in several studies, putting it up as a therapeutic candidate for bladder cancer. Network pharmacologic approaches is a high valuable tool in predicting rational drug targets within disease signaling module. Network based protein-protein interactome prediction, GO annotation and KEGG pathway enrichment analysis showed that prochlorperazine might affect bladder cancer growth through multiple signaling pathways. Cellular function experiments revealed that prochorperazine inhibited cell proliferation in several bladder cancer cell lines and in vivo mouse xenograft test confirmed its significant inhibition effect on BC. Western blotting analysis demonstrated that prochlorperazine treatment markedly modulated the expression and phosphorylation levels of MAPK1（ERK2）、MAP2K1（MEK1）and SRC, showing the possible molecular mechanism via the SRC-MEK-ERK pathway in BC cancer. These studies indicated the potential inhibitory impact of prochlorperazine and provided new ideas for the pathogenesis and treatments of BC.