Social Stress-induced Depression Of Mouse Lung And Icariin Intervention Study

Objective: Evaluate icariin's effect on tumor growth and metastasis of tumor and depression coexistence model. Explore icariin's intervention targets on tumor and depression coexistence model. Method: 1. Tumor and depression coexistence model were treated with icariin. Tumor weight and lung metastatic nodules were calculated; Tumor tissue's VEGF, CD11b and MVD were tested by immunohistochemistry; MDSC were measured by flow cytometry; Serum VEGF and IL-6 were detceted by ELISA. 2. Social stress-induced depression model were treated with icariin .The residence time at interation zone was recorded by MED behavior analysis system; Serum corticosterone and IL-6 were tested by ELISA; GR was detected by radioative ligand method and western blot. 3. Inflammation model stimulated by lipopolysaccharide were treated with icariin and its metabolites (icaritin and icariside) . TNF-α, IL-6 and PGE2 were measured by ELISA; NO was detected by Griess Reagent method. iNOS and COX2 were tested by western blot; CD11b were measured by flow cytometry. 4. LLC tumor model and angiogenesis model were treated with icariin and its metabolites . In vitro experiment: LLC cell proliferation was tested by cell counting kit-8; LLC cell cycle was measured by flow cytometry; Apoptosis was observed by Tunel method; HUVEC and CAM were used as angiogenesis models to evaluate anti-angiogenesis effect .In vivo experiment: Tumor weight and lung metastasis nodules were calculated; Tumor tissue's VEGF and MVD were tested by immunohistochemistry; MDSC was measured by flow cytometry ; Serum VEGF and IL-6 were detected by ELISA. Results: 1. Social stress induced depression promoted tumor growth and metastasis. Icariin treated this tumor and depression coexistence model effectively. It reduced the MDSC, CD11b, IL-6, VEGF and MVD levels. 2. Icariin treated social stress model effectively .It increased depression mice residence time at interation zone, reduced the level of corticosterone and IL-6, and restored GR protein expression and binding activity. 3. Icariin and its metabolity ( icaritin) inhibited the inflammatory model stimulated by LPS effectively. It reduced TNF-α, IL-6, PGE2, NO, CD11b levels and expression of iNOS and C0X2. 4. Icarisde displayed cytotoxicity, cycle arrest and apoptosis effect on LLC, while icaritin showed anti-angiogenesis effect in vitro. Icariin can inhibit tumor growth and metastasis in vivo effectively. Conclusion: 1. Social stress-induced depression can promote tumor growth and metastasis dramatically, and exacerbate the immune suppression,inflammation and angiogenesis. Icariin can intervene the above process .2. Icariin displayed anti-depression ,anti- inflammatory, anti-tumor effects, respectively. These effect can benefit cancer patients with depression. 3. Icarisde and icaritin may be the major in vivo active ingredients of icariin.