目的研究原发性肝细胞癌(pri mary hepatocellular carcinoma,PHC)组织中多药耐药基因P-糖蛋白(P-glycoprotein,P-gp)、拓扑异构酶Ⅱα(topoisomeraseⅡalpha,TopoⅡα)和P53的表达及共表达情况,分析其表达与PHC临床特征的关系。方法采...目的研究原发性肝细胞癌(pri mary hepatocellular carcinoma,PHC)组织中多药耐药基因P-糖蛋白(P-glycoprotein,P-gp)、拓扑异构酶Ⅱα(topoisomeraseⅡalpha,TopoⅡα)和P53的表达及共表达情况,分析其表达与PHC临床特征的关系。方法采用免疫组织化学SP法检测P-gp、TopoⅡα和P53的表达,并结合临床特征进行分析。结果 P-gp、TopoⅡα和P53阳性表达率分别为80.74%(109/135)、46.67%(63/135)和33.33%(45/135),P-gp阳性率明显高于TopoⅡα、P53(P=0.000),TopoⅡα阳性率高于P53(P<0.05)。P-gp阳性率与患者年龄、肿瘤细胞分化程度、肿瘤大小有关,患者血清AFP升高者P-gp、TopoⅡα阳性率均高于AFP正常者(P<0.05),血清AST升高者P-gp、P53阳性率均高于AST正常者(P<0.05)。TopoⅡα和P53阳性率与患者年龄、肿瘤细胞分化程度、肿瘤大小无关(P>0.05)。两种和三种基因产物共表达阳性率为51.85%(70/135),明显高于单一基因产物表达阳性率34.07%(χ2=8.706,P<0.01)。结论肝癌多药耐药是由多种耐药基因产物共同作用的结果,单基因和多基因共同作用,以多基因共表达为主。联合检测肝癌患者的多药耐药基因产物,对于临床合理用药、提高化疗疗效具有指导意义。展开更多
Background:TopoisomeraseⅡalpha(TOP2A)has been reported to play a crucial role in the tumorigenesis of various cancer types.However,the biological role of TOP2A in gallbladder cancer(GBC)remains unknown.The current st...Background:TopoisomeraseⅡalpha(TOP2A)has been reported to play a crucial role in the tumorigenesis of various cancer types.However,the biological role of TOP2A in gallbladder cancer(GBC)remains unknown.The current study aimed to explore the function and potential mechanism of TOP2A in GBC.Methods:Based on Gene Expression Profiling Interactive Analysis data,we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival.Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues.In vitro,cell proliferation,migration,and invasion ability were examined by cell counting kit-8 and transwell assay,respectively.Epithelial-mesenchymal transition(EMT)related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway-related markers were measured by Western blotting.Xenograft model assay was performed to evaluate the effect of TOP2A in vivo.Results:TOP2A was found up-regulated in GBC(tumor vs.normal,12.62 vs.0.34)and correlated with the late tumor node metastasis stage(P=0.0032),present of lymph node metastasis(P=0.0273),and poor prognosis in GBC patients(log-rank P=0.028).In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation,migration,invasion,EMT process,and tumor growth in GBC.In addition,TOP2A down-regulation significantly decreased the protein levels of phosphor(p)-PI3K,p-Akt,and p-mTOR.Conclusion:Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients.TOP2A promotes GBC cell proliferation,migration,invasion,EMT process,and tumor growth through activating PI3K/Akt/mTOR signaling pathway,and may serve as a novel prognostic biomarker and therapeutic target for GBC.展开更多
文摘目的研究原发性肝细胞癌(pri mary hepatocellular carcinoma,PHC)组织中多药耐药基因P-糖蛋白(P-glycoprotein,P-gp)、拓扑异构酶Ⅱα(topoisomeraseⅡalpha,TopoⅡα)和P53的表达及共表达情况,分析其表达与PHC临床特征的关系。方法采用免疫组织化学SP法检测P-gp、TopoⅡα和P53的表达,并结合临床特征进行分析。结果 P-gp、TopoⅡα和P53阳性表达率分别为80.74%(109/135)、46.67%(63/135)和33.33%(45/135),P-gp阳性率明显高于TopoⅡα、P53(P=0.000),TopoⅡα阳性率高于P53(P<0.05)。P-gp阳性率与患者年龄、肿瘤细胞分化程度、肿瘤大小有关,患者血清AFP升高者P-gp、TopoⅡα阳性率均高于AFP正常者(P<0.05),血清AST升高者P-gp、P53阳性率均高于AST正常者(P<0.05)。TopoⅡα和P53阳性率与患者年龄、肿瘤细胞分化程度、肿瘤大小无关(P>0.05)。两种和三种基因产物共表达阳性率为51.85%(70/135),明显高于单一基因产物表达阳性率34.07%(χ2=8.706,P<0.01)。结论肝癌多药耐药是由多种耐药基因产物共同作用的结果,单基因和多基因共同作用,以多基因共表达为主。联合检测肝癌患者的多药耐药基因产物,对于临床合理用药、提高化疗疗效具有指导意义。
文摘Background:TopoisomeraseⅡalpha(TOP2A)has been reported to play a crucial role in the tumorigenesis of various cancer types.However,the biological role of TOP2A in gallbladder cancer(GBC)remains unknown.The current study aimed to explore the function and potential mechanism of TOP2A in GBC.Methods:Based on Gene Expression Profiling Interactive Analysis data,we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival.Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues.In vitro,cell proliferation,migration,and invasion ability were examined by cell counting kit-8 and transwell assay,respectively.Epithelial-mesenchymal transition(EMT)related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway-related markers were measured by Western blotting.Xenograft model assay was performed to evaluate the effect of TOP2A in vivo.Results:TOP2A was found up-regulated in GBC(tumor vs.normal,12.62 vs.0.34)and correlated with the late tumor node metastasis stage(P=0.0032),present of lymph node metastasis(P=0.0273),and poor prognosis in GBC patients(log-rank P=0.028).In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation,migration,invasion,EMT process,and tumor growth in GBC.In addition,TOP2A down-regulation significantly decreased the protein levels of phosphor(p)-PI3K,p-Akt,and p-mTOR.Conclusion:Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients.TOP2A promotes GBC cell proliferation,migration,invasion,EMT process,and tumor growth through activating PI3K/Akt/mTOR signaling pathway,and may serve as a novel prognostic biomarker and therapeutic target for GBC.