1.GANT61 as an inhibitor of Gli inhibits growth and invasion of esophageal adenocarcinoma
Lei WANG ; Yuankun DU ; Lin WANG ; Yuan MI ; Haijiang LIAO
Tianjin Medical Journal 2016;44(5):556-559
Objective To study the inhibitory effects of GANT61, as an inhibitor of Gli, on the growth of human esophageal adenocarcinoma cell lines OE19 and OE33, and their mechanisms thereof. Methods After treating with different concentrations of GANT61(30,20,13.333 3,8.888 8,5.925 9,3.950 6,2.633 7,1.755 8,1.170 5μmol/L),the cell viabilities of OE19 and OE33 were detected by MTS method, which expressed by IC50. The Gli1and Gli2 mRNA expressions treated with GANT61(10 μmol/L GANT61) or DMSO for 24 h were detected in OE19 and OE33 cell lines by real time fluorescence quantitative PCR. The protein expressions of Gli1, Gli2 and CyclinD1 treated with GANT61 or DMSO for 24 h were detected in OE19 and OE33 cell lines by Western blot assay. Transwell invasion assay was performed to evaluate the inhibiting effect on OE19 and OE33 cell invasion by the treatment of GANT61 or DMSO. Results The IC50 of GANT61 was 8.08μmol/L in OE19 and 9.65μmol/L in OE33 cells. Compared with DMSO group, Gli1 and Gli2 mRNA expressions and Gli1,Gli2 and CyclinD1 protein expressions were significantly decreased in OE19 and OE33 cells of GANT61 group (P<0.05). The number of penetrating cells was significantly reduced in OE19 and OE33 cells of GANT61 group compared with that of DMSO group (P<0.01). Conclusion GANT61 can inhibit the growth and invasion of esophageal neoplasms cells by down-regulating Gli1 and Gli2 mRNA expression,which indicates that Hedgehog signaling pathway may play an important role in carcinogenesis and progression of esophageal adenocarcinoma.
2.Crosstalk of Hedgehog/Gli and PI3k/Akt Pathway Promotes Epithelial-mesenchymal Transition in Gastric Adenocarcinoma
Lei WANG ; Yuankun DU ; Yuan MI ; Haijiang LIAO ; Ge CHEN ; Yaozhong ZHANG ; Qingyi LIU
Journal of China Medical University 2018;47(2):151-156
Objective To investigate the tumor molecular mechanism of Hedgehog/Gli in promoting the epithelial-mesenchymal transition (EMT) in gastric cancer AZ521 cells. Methods After 24 h of treatment with GANT61,the mRNA expression of Gli1,Gli2, N-cadherin,and E-cadherin in the AZ521 cell line were detected by real-time fluorescence quantitative PCR. A Western blotting assay was conducted to determine the expression of the above cytokines,p-AKT and AKT. The effect of GANT61 on invasion was observed by transwell assay. N-Shh stimulation of the Hedgehog pathway was conducted to confirm the changes in these cytokines. Results GANT61 significantly downregulated the mRNA expression of Gli1,Gli2,and N-cadherin,but upregulated E-cadherin mRNA expression. The Western blotting assay revealed that GANT61 downregulated the protein expression of Gli1,Gli2,p-AKT,and N-cadherin,but upregulated E-cadherin expression. Furthermore,GANT61 inhibited the invasion. N-Shh proteins up-regulated Gli1,Gli2,and N-cadherin mRNA,protein expression and p-AKT protein expression,but downregulated E-cadherin mRNA and protein expressions. N-Shh promoted the invasion of tumor cells. Conclusion Downregulation of Gli1 and Gli2 can inhibit the invasion and metastasis in gastric cancer cells,which may be related to the promotion of EMT by Gli through the PI3K/AKT pathway.
3.Effect of visceral fat area on the prognosis of patients with radical gastrectomy
Xiaowen LI ; Guanglin QIU ; Haijiang WANG ; Panxing WANG ; Jiahuang LIU ; Mengke ZHU ; Xinhua LIAO ; Lin FAN ; Xiangming CHE
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(3):419-425
【Objective】 To investigate the predictive value of visceral fat area (VFA) in patients with gastric cancer after radical gastrectomy. 【Methods】 A retrospective analysis was performed on 195 patients who underwent radical gastrectomy in the Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University from January 2014 to December 2017. CT image data and clinicopathological data within 1 week before surgery were collected. VFA was calculated by software, and the patients were divided into VFA-H group (n=96) and VFA-L group (n=99). The relationship between VFA in different groups and long-term prognosis was compared. 【Results】 CT examination results showed that VFA value was (111±62) cm2, and BMI was positively correlated with VFA value (r=0.640, P<0.001). ROC curve showed that VFA was more valuable in predicting the prognosis of gastric cancer (AUC=0.703, P<0.001) and better than BMI. Cox regression analysis of prognostic factors in gastric cancer patients: Univariate analysis showed that age, tumor length, TNM stage and VFA were the influencing factors for prognosis, while multivariate analysis showed that TNM stage III and VFA-L were independent risk factors for prognosis of gastric cancer patients. 【Conclusion】 VFA has a good predictive ability and can be used to evaluate the prognosis of gastric cancer patients after operation.