BACKGROUND Gallbladder cancer(GBC)is an aggressive type of biliary tract cancer that lacks effective therapeutic targets.Fork head box M1(FoxM1)is an emerging molecular target associated with tumor progression in GBC,...BACKGROUND Gallbladder cancer(GBC)is an aggressive type of biliary tract cancer that lacks effective therapeutic targets.Fork head box M1(FoxM1)is an emerging molecular target associated with tumor progression in GBC,and accumulating evidence suggests that vascular endothelial growth factor(VEGF)promotes various tumors by inducing neoangiogenesis.AIM To investigate the role of FoxM1 and the angiogenesis effects of VEGF-A in primary GBC.METHODS Using immunohistochemistry,we investigated FoxM1 and VEGF-A expression in GBC tissues,paracarcinoma tissues and cholecystitis tissues.Soft agar,cell invasion,migration and apoptosis assays were used to analyze the malignant phenotype influenced by FoxM1 in GBC.Kaplan-Meier survival analysis was performed to evaluate the impact of FoxM1 and VEGF-A expression in GBC patients.We investigated the relationship between FoxM1 and VEGF-A by regulating the level of FoxM1.Next,we performed MTT assays and Transwell invasion assays by knocking out or overexpressing VEGF-A to evaluate its function in GBC cells.The luciferase assay was used to reveal the relationship between FoxM1 and VEGF-A.BALB/c nude mice were used to establish the xenograft tumor model.RESULTS FoxM1 expression was higher in GBC tissues than in paracarcinoma tissues.Furthermore,the high expression of Foxm1 in GBC was significantly correlated with a malignant phenotype and worse overall survival.Meanwhile,high expression of FoxM1 influenced angiogenesis;high expression of FoxM1 combined with high expression of VEGF-A was related to poor prognosis.Attenuated FoxM1 significantly suppressed cell proliferation,transfer and invasion in vitro.Knockdown of FoxM1 in GBC cells reduced the expression of VEGF-A.Luciferase assay showed that FoxM1 was the transcription factor of VEGF-A,and knockdown VEGF-A in FoxM1 overexpressed cells could partly reverse the malignancy phenotype of GBC cells.In this study,we found that FoxM1 was involved in regulation of VEGF-A expression.CONCLUSION FoxM1 and VEGF-A overexpression were associated with the prognosis of GBC patients.FoxM1 regulated VEGF-A expression,which played an important role in the progression of GBC.展开更多
目的:探讨术前血清叉头框蛋白O1(Fork head box protein O1,FoxO1)和脂肪酸转运蛋白4(fatty acid-binding protein 4,FABP4)与非肌层浸润性膀胱癌(Non-muscle invasive bladder cancer,NMIBC)患者灌注治疗疗效的关系。方法:选取2021年1...目的:探讨术前血清叉头框蛋白O1(Fork head box protein O1,FoxO1)和脂肪酸转运蛋白4(fatty acid-binding protein 4,FABP4)与非肌层浸润性膀胱癌(Non-muscle invasive bladder cancer,NMIBC)患者灌注治疗疗效的关系。方法:选取2021年1月至2022年10月期间本院收治的68例NMIBC患者作为研究对象。所有患者进行经尿道膀胱肿瘤切除术(Transurethral resection of bladder tumor,TURBT)治疗,患者术后给予表柔比星膀胱灌注。随访12 m,根据最终的病理结果,将患者分为复发组和未复发组。检测对比两组术前血清FOXO1水平和FABP4水平。分析术前血清FABP4水平与TURBT术后膀胱灌注疗效的相关性及诊断价值。结果:68例患者TURBT术后给予表柔比星膀胱灌注,复发率22.1%。复发组术前血清FOXO1水平与未复发组无明显差异(P>0.05);复发组术前血清FABP4水平显著高于未复发组(P<0.05)。以术前血清FABP4水平预测TURBT术后给予表柔比星膀胱灌注治疗后复发的AUC=0.7052。结论:术前血清高FABP4水平提示TURBT术后给予表柔比星膀胱灌注治疗易复发,其用来预测表柔比星膀胱灌注治疗效果有较高价值。展开更多
基金Scientific and Technological Development Research Project Foundation of Shaanxi Province of China,No.2020SF-069.
文摘BACKGROUND Gallbladder cancer(GBC)is an aggressive type of biliary tract cancer that lacks effective therapeutic targets.Fork head box M1(FoxM1)is an emerging molecular target associated with tumor progression in GBC,and accumulating evidence suggests that vascular endothelial growth factor(VEGF)promotes various tumors by inducing neoangiogenesis.AIM To investigate the role of FoxM1 and the angiogenesis effects of VEGF-A in primary GBC.METHODS Using immunohistochemistry,we investigated FoxM1 and VEGF-A expression in GBC tissues,paracarcinoma tissues and cholecystitis tissues.Soft agar,cell invasion,migration and apoptosis assays were used to analyze the malignant phenotype influenced by FoxM1 in GBC.Kaplan-Meier survival analysis was performed to evaluate the impact of FoxM1 and VEGF-A expression in GBC patients.We investigated the relationship between FoxM1 and VEGF-A by regulating the level of FoxM1.Next,we performed MTT assays and Transwell invasion assays by knocking out or overexpressing VEGF-A to evaluate its function in GBC cells.The luciferase assay was used to reveal the relationship between FoxM1 and VEGF-A.BALB/c nude mice were used to establish the xenograft tumor model.RESULTS FoxM1 expression was higher in GBC tissues than in paracarcinoma tissues.Furthermore,the high expression of Foxm1 in GBC was significantly correlated with a malignant phenotype and worse overall survival.Meanwhile,high expression of FoxM1 influenced angiogenesis;high expression of FoxM1 combined with high expression of VEGF-A was related to poor prognosis.Attenuated FoxM1 significantly suppressed cell proliferation,transfer and invasion in vitro.Knockdown of FoxM1 in GBC cells reduced the expression of VEGF-A.Luciferase assay showed that FoxM1 was the transcription factor of VEGF-A,and knockdown VEGF-A in FoxM1 overexpressed cells could partly reverse the malignancy phenotype of GBC cells.In this study,we found that FoxM1 was involved in regulation of VEGF-A expression.CONCLUSION FoxM1 and VEGF-A overexpression were associated with the prognosis of GBC patients.FoxM1 regulated VEGF-A expression,which played an important role in the progression of GBC.
文摘目的:探讨术前血清叉头框蛋白O1(Fork head box protein O1,FoxO1)和脂肪酸转运蛋白4(fatty acid-binding protein 4,FABP4)与非肌层浸润性膀胱癌(Non-muscle invasive bladder cancer,NMIBC)患者灌注治疗疗效的关系。方法:选取2021年1月至2022年10月期间本院收治的68例NMIBC患者作为研究对象。所有患者进行经尿道膀胱肿瘤切除术(Transurethral resection of bladder tumor,TURBT)治疗,患者术后给予表柔比星膀胱灌注。随访12 m,根据最终的病理结果,将患者分为复发组和未复发组。检测对比两组术前血清FOXO1水平和FABP4水平。分析术前血清FABP4水平与TURBT术后膀胱灌注疗效的相关性及诊断价值。结果:68例患者TURBT术后给予表柔比星膀胱灌注,复发率22.1%。复发组术前血清FOXO1水平与未复发组无明显差异(P>0.05);复发组术前血清FABP4水平显著高于未复发组(P<0.05)。以术前血清FABP4水平预测TURBT术后给予表柔比星膀胱灌注治疗后复发的AUC=0.7052。结论:术前血清高FABP4水平提示TURBT术后给予表柔比星膀胱灌注治疗易复发,其用来预测表柔比星膀胱灌注治疗效果有较高价值。
