1. Digestive Pathophysiology of Zhejiang Province, the First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou, 310006, China
2. College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, 310006, China
3. Institute of Basic Theory of TCM, China Academy of Chinese Medical Sciences, Beijing 100700, China
4. Bioinformatics and Drug Design Group, Department of Pharmacy and Center for Computational Science and Engineering, National University of Singapore, 117543, Singapore
5. Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diagnosis and Treatment of Digestive System Tumor, the First Affiliated Hospital of Zhejiang Chinese Medical University,54 Youdian Road, Hangzhou, 310006, China
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.
Keywords: gastric cancer, sertindole, cell apoptosis, cisplatin