Brexpiprazole Prevents the Malignant Progression of Human Colorectal Cancer Cells and Increases Its Sensitivity to EGFR Inhibition

Background : Colorectal cancer (CRC) is a major cause of mortality and morbidity. A study proved that brexpiprazole, as a novel dopamine receptor partial agonist, can also prevent CRC cell proliferation. Therefore, clarifying the molecular mechanism of brexpipra-zole is vital to developing a novel therapeutic strategy for CRC. Methods : The effect of brexpiprazole on human colorectal cancer cell proliferation was measured with Cell Counting Kit-8 (CCK-8) kits. Cell migration capability was measured using wound healing and transwell. Cell apoptosis was evaluated with a flow cytometer. Western blots and immunohistochemical staining were used to evaluate protein expression. The effects observed in vitro were also confirmed in xenograft models. Results : Brexpiprazole remarkably inhibited the proliferation, suppressed the migration ability, and induced apoptosis of colorectal cancer cells. Mechanism study showed that brex-piprazole exerted these effects by inhibiting the EGFR pathway. Brexpiprazole enhanced HCT116 cells’ sensitivity to cetuximab, and a combination of brexpiprazole and cetuximab inhibited xenograft tumor growth in vivo . Conclusions : Our finding suggested that brex-piprazole inhibits proliferation, promotes apoptosis, and enhances CRC cells’ sensitivity to cetuximab by regulating the EGFR pathway and it might be an efficacious treatment strategy for CRC.