顺铂联合氟西汀对肺癌伴抑郁小鼠干预的研究

Interventional effect of cisplatin combined with fluoxetine on mice bearing Lewis lung cancer with depression

目的通过顺铂联合氟西汀对肺癌伴抑郁小鼠进行干预,检测相关指标,观察氟西汀能否通过抗抑郁作用对肿瘤起到抑制作用。方法通过社交失败应激及皮下接种Lewis肺癌细胞株建立小鼠肺癌伴抑郁模型;ELISA方法检测血清皮质醇及IL-6水平;RT-PCR方法检测海马组织中脑源性神经营养因子(brain derived neurotropic factor,BDNF)mRNA表达;免疫组织化学方法检测肿瘤组织核转录因子-κB(nuclear factor-κB,NF-κB)及血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白表达。结果双药组皮质醇与IL-6水平与模型组相比明显降低(P<0.05);双药组海马BDNF mRNA表达显著升高(P<0.05);双药组肿瘤重量、肿瘤组织中NF-κB及VEGF蛋白表达水平与单药组相比差异无显著性(P>0.05)。结论氟西汀能够降低肺癌伴抑郁小鼠血清皮质醇水平并促进海马组织BDNF mRNA表达而发挥抗抑郁作用,但并未发现其抗抑郁效果能够抑制肿瘤进展。

Objective To observe if fluoxetine has a potency to inhibit the progression of Lewis lung cancer by combining the fluoxetine and cisplatin to treat the mice bearing Lewis lung cancer with depression. Methods We developed a mouse model of Lewis lung cancer with depression which was intervened with cisplatin and fluoxetine,and the indicators related to cancer and depression were tested. Social interaction test was used to measure the behavioral changes of the depressed model mice. The serum cortisol and IL-6,BDNF mRNA in the hippocampus,and NF-κB and VEGF in the tumor tissue were selected for investigation and comparison. Results The mice which were induced by social defeat exhibited social avoidance behavior in the social interaction test. The cortisol and IL-6 level in both combination groups was decreased compared with that in the model group( P < 0. 05),and the cortisol and BDNF mRNA in the combination group increased signifuicantly( P < 0. 05). There were no statistically significant differences in the tumor weight,NF-κB and VEGF in tumor tissues between the single and combination groups( P > 0. 05). Conclusions Fluoxetine has antidepressant effect by decreasing the high level of serum cortisol and promoting the BDNF mRNA expression in the hippocampus.However,fluoxetine is not found to have the potency to inhibit the expression of NF-κB related with the progression of tumor.