摘要
Abstract
Objective To investigate the effect of Ghrelin on cellular proliferation and invasion of colon carcinoma and potential mechanisms.Methods A total of 90 patients diagnosed with colon carcinoma were included in this study,and cancer as well as paracancerous normal tissue was collected.Expression of Ghrelin was measured by Immunohistochemical staining assay;Co-relationship analysis between ghrelin expression and clinical manifestation of patients including survival rate was performed.Expression of Ghrelin in colon carcinoma cell line HT29 and SW480 was genetically inhibited by short hairpin RNA (shRNA).Cellular proliferation,cell cycle as well as apoptosis,migration,and cell invasion were determined by CCK-8 assay,Flow cytometry,Wound heal assay,and Transwell assay,respectively.Expression levels of PI3K,Akt,p-Akt,mTOR,p-mTOR protein were measured by Western blot.Results Expression of Ghrelin in cancer tissue,group with tumor diameter ≥ 5 cm,and group with tumor under Ⅲ～ Ⅳ phase was upregulated when compared with that in paracancerous tissue,group with tumor diameter ＜ 5 cm group,group with tumor under metastasis-free phase,respectively (P ＜ 0.05).No correlation between Ghrelin expression and gender,age and tumor grade respectively was observed (P ＞ 0.05).Overall survival and disease-free survival in group with highly expressed Ghrelin was significantly lower than that in group with lowly expressed Ghrelin (P ＜ 0.05).Proliferation,migration and invasion capacity of HT29 and SW480 cells decreased while ratio of cells in S phase and early apoptosis increased significantly in sh-Ghrelin group when compared with those in NC group and WT group (P ＜ 0.05).In HT29 and SW480 cells expression levels of PI3K,p-Akt,p-mTOR protein were dramatically down-regulated in sh-Ghrelin group when compared with those in NC group and WT group (P＜ 0.05).No statistical difference in the expression of PI3K,Akt,p-Akt,mTOR,p-mTOR protein in NC group and WT group was observed (P ＞ 0.05).Conclusions The expression of Ghrelin is up-regulated in colon carcinoma tissue,which is closely associated with disease prognosis.Beneficial effect of Ghrelin is potentially mediated through inhibition of PI3K-Akt-mTOR signaling pathway.关键词
胃饥饿素/结肠癌/增殖/细胞周期/侵袭/信号通路Key words
Ghrelin/colon carcinoma/proliferation/cell cycle/invasion/signaling pathway分类
医药卫生
