Wee1 Inhibitor AZD1775 Combined with Cisplatin Potentiates Anticancer Activity against Gastric Cancer by Increasing DNA Damage and Cell Apoptosis

Abstract

Based on the mechanisms by which Wee1 inhibitor and cisplatin played their own role, a promising strategy of Wee1 inhibitor combined with cisplatin was proposed, which was investigated in gastric cancer (GC). Either Wee1 inhibitor AZD1775 or cisplatin alone had a certain inhibitory effect on in vitro cell proliferation; however, the inhibitory effect was more significant when AZD1775 combined with cisplatin in vitro and in vivo. The underlying mechanisms unveiled that the increased DNA damage indicated by increased γH2AX protein, as well as augmented cell apoptosis indicated by upregulated proapoptotic proteins, was responsible for the significant inhibitory effect of AZD1775 plus cisplatin. Moreover, compared to any single drug, in vitro cell migration and invasion abilities were further attenuated by AZD1775 combined with cisplatin. There were suggestive results that the potentiated cytotoxicity between AZD1775 and cisplatin deserved a deep exploration in the future.