Association of Risperidone With Gastric Cancer: Triangulation Method From Cell Study, Animal Study, and Cohort Study

<jats:p><jats:bold>Purpose:</jats:bold> To examine the effects of risperidone, an atypical antipsychotic agent, on gastric cancer.</jats:p><jats:p><jats:bold>Methods:</jats:bold> A triangulation method comprising bench studies, including cell and animal experiments, and a retrospective cohort study, was subsequently performed.</jats:p><jats:p><jats:bold>Results:</jats:bold> The bench study indicated that risperidone exerted more prominent tumor inhibition effects than other atypical antipsychotics on the proliferation of KATO-III cells, a human gastric cancer cell line. Significant and dose-dependent cell viability was observed in Hs27 cells (control cells) in the presence of risperidone compared with in KATO-III cells. Both <jats:italic>in vivo</jats:italic> and <jats:italic>in vitro</jats:italic> results indicated that risperidone significantly inhibited the proliferation of KATO-III cells by inducing ROS and apoptosis, and that it suppressed the growth of xenografted KATO-III tumors in nude mice. In addition, the population-based cohort study found that risperidone users had reduced risks of gastric cancer compared with non-users, with lowered adjusted hazard ratios (HRs) for two induction periods (HR = 0.75; 95% confidence interval [CI] 0.68–0.83 for the one-year induction period, and HR = 0.68; 95% CI 0.61–0.75 for the two-year induction period).</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> The findings are consistent with anticancer effects associated with risperidone, but further research and evaluations are warranted.</jats:p>