Die durch chronischen Stress induzierte massive Verschlechterung der Prognose beim Pankreaskarzinom kann durch β-Blocker signifikant verbessert werden

Abstract

Introduction. Chronic stress induces a massive immunosuppression. This might lead to an impaired prognosis in pancreatic cancer. Here we have studied the underlying mechanism and possible therapeutic strategies of chronic stress in a murine pancreatic cancer model. Materials and Methods. In a murine orthotopic pancreatic cancer model mice were treated by combined chronic acoustic and restraint stress. The level of stress and/or immunosuppression was measured by stress parameters: behaviour of animals, levels of corticosterone, sizes of adrenal glands, levels of tyrosine hydroxylase as well as concentrations of several cytokines. In vitro stress hormone experiments tested the impact of catecholamines on proliferation and invasion of tumour cells. During stress trials murine tumour growth and survival were monitored. Also, these were the most important parameters when analyzing the effects of beta blocker treatment. Results. All parameters of stress were significantly elevated following stress application. Also, chronic stress induced immunosuppression (p 0.05). This was significantly inhibited by the oral application of beta blockers. Furthermore, chronic stress led to a significant reduction of survival (52 versus 66 days, p < 0.0001). Again, oral beta blockers significantly improved survival of chronically stressed mice (59 versus 52 days, p < 0.005). Conclusions. Chronic stress can significantly reduce survival in cancer patients. This is mediated via catecholamines. The targeted therapy of chronic stress in pancreatic cancers patients using beta blockers may significantly improve their prognosis. This is a new therapeutic strategy in pancreatic cancer therapy.