Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isol...Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.展开更多
目的:探讨去整合素金属蛋白酶9(a disintegrin and metalloproteinase 9,ADAM9)蛋白在人乳腺癌细胞系中的表达。方法:提取人正常乳腺上皮细胞HBL100,人乳腺癌细胞系MCF-7,ZR-75-1,MDA-MB-231,HCC1937和Hs578T,小鼠乳腺癌细胞系4T1的总...目的:探讨去整合素金属蛋白酶9(a disintegrin and metalloproteinase 9,ADAM9)蛋白在人乳腺癌细胞系中的表达。方法:提取人正常乳腺上皮细胞HBL100,人乳腺癌细胞系MCF-7,ZR-75-1,MDA-MB-231,HCC1937和Hs578T,小鼠乳腺癌细胞系4T1的总蛋白和总mRNA,提取细胞的总蛋白和总RNA进行蛋白免疫印迹和实时定量PCR检测ADAM9的表达。结果:在人乳腺癌细胞系MDA-MB-231中ADAM9蛋白表达最高,在小鼠乳腺癌4T1细胞中ADAM9表达较低。结论:ADAM9在高侵袭的MDA-MB-231乳腺癌细胞中高表达。展开更多
去整合素–金属蛋白酶家族(adisintegrin and metalloproteinase, ADAMs)是一类锌依赖的跨膜糖蛋白,ADAMs家族分子具有相似的分子结构包括:结构域(单肽)末端金属域、整合素域、富含半胱氨酸的序列、膜近端上皮生长因子样序列。ADAM9在...去整合素–金属蛋白酶家族(adisintegrin and metalloproteinase, ADAMs)是一类锌依赖的跨膜糖蛋白,ADAMs家族分子具有相似的分子结构包括:结构域(单肽)末端金属域、整合素域、富含半胱氨酸的序列、膜近端上皮生长因子样序列。ADAM9在胶质瘤、黑色素瘤、前列腺癌、胰腺导管腺癌、胃癌、乳腺癌、肺癌和肝癌等实体肿瘤中均有过表达。免疫组织化学分析强调了ADAM9在实际癌细胞中的表达,并将其丰富的表达与临床病理特征联系起来,如总体生存期缩短、肿瘤分级较差、去分化、治疗耐药性和转移形成。本文综述了ADAM9在肿瘤中的研究现状,以及它在推动肿瘤进展方面的不同机制。展开更多
目的观察去整合素金属蛋白酶9(a disintegrin and metalloproteinase 9,ADAM9)在小鼠肾发育中的时空表达,从而探讨ADAM9与肾发育的关系。方法采用免疫组织化学结合体视学方法和免疫印迹法,测定胚龄11、14、16、18d及生后1、3、7、14、28...目的观察去整合素金属蛋白酶9(a disintegrin and metalloproteinase 9,ADAM9)在小鼠肾发育中的时空表达,从而探讨ADAM9与肾发育的关系。方法采用免疫组织化学结合体视学方法和免疫印迹法,测定胚龄11、14、16、18d及生后1、3、7、14、28、40d小鼠肾组织内ADAM9的表达以及含量变化。结果免疫组织化学显示ADAM9在输尿管芽以及各期肾小体、皮质肾小管均有表达,生后1d后髓质小血管有表达,集合管表达始终较弱;细胞图像分析和体视学测量显示随着胚日龄的增加,ADAM9在肾小体的表达逐渐增强,后趋于稳定;肾小管的表达则呈先增后减的趋势;免疫印迹显示ADAM9在肾的表达量在生后7d达到高峰,随后逐渐减弱。结论 ADAM9对肾的早期发育起重要作用。展开更多
The 'a disintegrin and metalloprotease' (ADAM) family contributes to regulation of the cell-cell and cell-matrix interactions that are critical determinants of malignancy. To determine the relationship between...The 'a disintegrin and metalloprotease' (ADAM) family contributes to regulation of the cell-cell and cell-matrix interactions that are critical determinants of malignancy. To determine the relationship between metastasis and ADAM proteins, we compared the mRNA levels of ADAM9,-10,-12,-15, and-17 in sublines of an EBC-1 lung cancer cell line that were highly metastatic to either brain or bone. ADAM9 mRNA levels were significantly higher in highly brain-metastatic sublines than in the parent or highly bonemetastalic sublines. To elucidate the role ofADAM9 in brain metastasis, we stably transfected A549 and EBC-1 cells with a fulllength ADAM9 expression vector. Compared with mock-transfectants, ADAM9 overexpression resulted in increased invasive capacity展开更多
基金supported by the National Science and Technology Council(NSTC 113-2320-B-039-049-MY3 and NSTC 114-2314-B-039-051-MY3)China Medical University(CMU113-ASIA-05,CMU-114-ASIA-01).
文摘Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.
文摘目的:探讨去整合素金属蛋白酶9(a disintegrin and metalloproteinase 9,ADAM9)蛋白在人乳腺癌细胞系中的表达。方法:提取人正常乳腺上皮细胞HBL100,人乳腺癌细胞系MCF-7,ZR-75-1,MDA-MB-231,HCC1937和Hs578T,小鼠乳腺癌细胞系4T1的总蛋白和总mRNA,提取细胞的总蛋白和总RNA进行蛋白免疫印迹和实时定量PCR检测ADAM9的表达。结果:在人乳腺癌细胞系MDA-MB-231中ADAM9蛋白表达最高,在小鼠乳腺癌4T1细胞中ADAM9表达较低。结论:ADAM9在高侵袭的MDA-MB-231乳腺癌细胞中高表达。
文摘去整合素–金属蛋白酶家族(adisintegrin and metalloproteinase, ADAMs)是一类锌依赖的跨膜糖蛋白,ADAMs家族分子具有相似的分子结构包括:结构域(单肽)末端金属域、整合素域、富含半胱氨酸的序列、膜近端上皮生长因子样序列。ADAM9在胶质瘤、黑色素瘤、前列腺癌、胰腺导管腺癌、胃癌、乳腺癌、肺癌和肝癌等实体肿瘤中均有过表达。免疫组织化学分析强调了ADAM9在实际癌细胞中的表达,并将其丰富的表达与临床病理特征联系起来,如总体生存期缩短、肿瘤分级较差、去分化、治疗耐药性和转移形成。本文综述了ADAM9在肿瘤中的研究现状,以及它在推动肿瘤进展方面的不同机制。
文摘The 'a disintegrin and metalloprotease' (ADAM) family contributes to regulation of the cell-cell and cell-matrix interactions that are critical determinants of malignancy. To determine the relationship between metastasis and ADAM proteins, we compared the mRNA levels of ADAM9,-10,-12,-15, and-17 in sublines of an EBC-1 lung cancer cell line that were highly metastatic to either brain or bone. ADAM9 mRNA levels were significantly higher in highly brain-metastatic sublines than in the parent or highly bonemetastalic sublines. To elucidate the role ofADAM9 in brain metastasis, we stably transfected A549 and EBC-1 cells with a fulllength ADAM9 expression vector. Compared with mock-transfectants, ADAM9 overexpression resulted in increased invasive capacity
