摘要
Abstract
Objective:To observe the influence of chronic obstructive pulmonary disease (COPD)-like chronic inflammation on the growth and metastasis of lung cancer through a mouse model,analyze the role of IL-1β,IL-6,TNF-α and IL-8 in the progression,and to find the probable signaling pathway.Methods:We selected male C57/BL6 mice aged 5-8 weeks,weighted 20-25 g to establish a COPD-like mouse model by smoking and instilled intratracheally with LPS.Lewis lung cancer cells (LLC) were implanted by directly puncturing through the skin and intercostal space into the lung to establish a lung cancer model,and implanted into the lung of COPD-like mouse to establish a COPD combined with lung cancer model.Methylprednisolone was injected into COPD combined with lung cancer model to establish a methylprednisolone-treated model.We observed and compared the tumor size and metastases number of COPD-lung cancer mouse model,lung cancer mouse model and methylprednisolone treated COPD-lung cancer mouse model.We detected the levels of IL-1β,IL-6,IL-8,TNF-α in serum by ELISA,and the expression of their mRNA in lung using real-time PCR in each group.And we also detected the expression of some probable signal molecule (Stat3,ERK1/2,NF-κB,and IκBα) in the lung of these 5 mice groups to find out the relative signaling pathway involved in the promoting process of chronic inflammation in COPD on the growth and metastasis of lung cancer.Results:Compared with lung cancer mice,the mice with lung cancer combined COPD had shorter median survival times,larger volumes of tumor nudes,and larger numbers of metastases,but if they were treated with methylprednisolone,all these changes come down,the differences were all statistically significant (P＜0.05).The levels of IL-1β,IL-6,IL-8 in the COPD-lung cancer mice serum were significantly higher than COPD mice without lung cancer and lung cancer mice without COPD (P＜0.05),and IL-6 increased much more sharply than other inflammatory cytokines in COPD-lung cancer mice,which increased about 2 times more than COPD mice and lung cancer mice,and 5 times more than control mice.In methylprednisolone-treated COPD-lung cancer mice,levels of all the inflammatory cytokines decreased.The activation ratios of Stat3,NF-κB,IκBα were significantly higher in COPD-lung cancer mice than control mice,COPD mice,and lung cancer mice (P＜0.05),and significantly lower in methylprednisolone-treated COPD-lung cancer mice than untreated (P＜0.05).Conclusion:The chronic inflammatory environment can promote the growth and metastasis of lung cancer,and then shorten the survival of lung cancer in our mouse model,controlling the inflammation using methylprednisolone can inhibit the promoting effect of COPD on lung cancer.IL-6 and IL-8 play roles in the promoting effect of chronic inflammation in COPD mice on the growth and metastasis of lung cancer.关键词
慢性阻塞性肺疾病/肺癌/小鼠模型/肿瘤生长转移/炎症细胞因子Key words
chronic obstructive pulmonary disease/lung cancer/mouse model/growth and metastasis/inflammatory cytokines
