biostudies-literatureLu JWu Jieping Medical FoundationNational Natural Science Foundation of ChinaNational Key Research and Development Program of China375https://www.ebi.ac.uk/biostudies/studies/S-EPMC11270788biostudies-literatureUnknown22(1)<h4>Background</h4>Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive.<h4>Methods</h4>Kras^LSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and Cell communication and signaling : CCSOlanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress.PMC11270788No. 823730962023HZ0602022YFA1104002No. 82273480Wang CMeng PKelley KWLiu QSu KLv DLuo HZhao ZWang LLiu XPeng FYang YLu JZhang XLiu CWang XHe BCui BfalseOlanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress.<h4>Background</h4>Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive.<h4>Methods</h4>Kras^LSL-G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and 2024-01-01T00:00:00Z2024 Jul2026-06-01T09:03:03.739Z2025-08-31T03:04:52.327ZS-EPMC112707883905453710.1186/s12964-024-01747-y