The Antipsychotic Agent Sertindole Exhibited Antiproliferative Activities by Inhibiting the STAT3 Signaling Pathway in Human Gastric Cancer Cells.

Abstract

Gastric cancer (GC) is the third leading cause of cancer-related death. Although the therapeutic approaches have improved, the 5-year survival rate of GC patients after surgical resection remains low due to the high rates of metastasis and recurrence. Patients with schizophrenia have significantly lower incidences of cancer after long-term drug treatment, suggesting the potential or partially ameliorate the risk of cancer development of antipsychotic drugs. The goal of this study was to explore antipsychotic drugs with an optional effective therapy against gastric cellular carcinoma. We found that sertindole, an atypical antipsychotic, exhibited anti-tumor efficacy on human GC cells in vitro and in vivo. Moreover, sertindole in combination with cisplatin dramatically enhanced apoptosis-induction in GC cells. In addition, the pro-apoptotic effect of sertindole on GC might in part, involved in inhibition of STAT3 activation and downstream signals, including Mcl1, surviving, c-Myc, cyclin D1. Collectively, these results suggested that sertindole could be a potential anticancer reagent and be an attractive therapeutic adjuvant for the treatment of human GC.