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基于网络药理学和细胞实验探讨Hispolon抗结肠癌的作用机制 被引量:4
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作者 李俊峰 吴力超 +4 位作者 王进 孙腾飞 赵俊慧 张婷婷 刘文洪 《中国药理学通报》 CAS CSCD 北大核心 2021年第8期1151-1158,共8页
目的运用网络药理学预测和细胞实验探讨Hispolon抗结肠癌的作用机制。方法Swiss Target Prediction网站获取Hispolon的潜在靶点,与疾病数据库GeneCards、OMIM中结肠癌靶点取交集;利用STRING11.0数据库构建靶点相互作用网络,使用Cytoscap... 目的运用网络药理学预测和细胞实验探讨Hispolon抗结肠癌的作用机制。方法Swiss Target Prediction网站获取Hispolon的潜在靶点,与疾病数据库GeneCards、OMIM中结肠癌靶点取交集;利用STRING11.0数据库构建靶点相互作用网络,使用Cytoscape3.7.2软件挖掘Hispolon作用于结肠癌的核心靶点,通过Metascape数据库进行GO和KEGG富集分析,最后采用Western blot验证Hispolon对结肠癌细胞SW480中部分关键靶点的调控作用。结果筛选出Hispolon抗结肠癌作用靶点69个,核心靶点包括BCL-2L1、EP300、CDK1、AR、MTOR、EGFR;富集分析发现Hispolon通过调节癌症相关通路、PI3K-Akt信号通路、前列腺癌相关通路等发挥抗结肠癌作用,并且通路中关键靶点涉及BCL-2L1、EP300、CDK1、MTOR和EGFR核心靶点。通过细胞实验证实Hispolon可下调靶点蛋白BCL-2L1和mTOR的表达,促进SW480细胞凋亡。结论Hispolon治疗结肠癌,具有多靶点、多通路协同作用的特点,该研究为进一步阐明Hispolon抗结肠癌作用机制及临床应用提供科学依据。 展开更多
关键词 Hispolon 结肠癌 网络药理学 作用机制 细胞实验 bcl-2l1 MTOR
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双荧光素酶报告基因系统验证hsa-miR-326对BCL2L1、BAK1的靶向调控 被引量:3
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作者 俞石芳 李强 +2 位作者 洪俊英 金陈华 陈碧乐 《中国卫生检验杂志》 北大核心 2014年第8期1156-1158,共3页
目的构建psiCHECK2荧光素酶报告基因载体,验证hsa-miR-326对BCL2L1和BAK1表达的影响。方法设计合成包含与hsa-miR-326结合序列及其突变型序列的BCL2L1和BAK1基因片段,构建荧光素酶报告基因载体,转染293T细胞,通过荧光素酶活性变化观察hs... 目的构建psiCHECK2荧光素酶报告基因载体,验证hsa-miR-326对BCL2L1和BAK1表达的影响。方法设计合成包含与hsa-miR-326结合序列及其突变型序列的BCL2L1和BAK1基因片段,构建荧光素酶报告基因载体,转染293T细胞,通过荧光素酶活性变化观察hsa-miR-326对BCL2L1和BAK1表达的影响。结果 hsa-miR-326对BCL2L1组的荧光表达有非常显著的抑制作用(P<0.01);而对BCL2L1-mut、BAK1和BAK1-mut组的荧光表达没有显著的抑制作用(P>0.05)。结论 hsa-miR-326可以调控BCL2L1的表达,但对BAK1的表达未见影响,推测hsa-miR-326可能通过下调BCL2L1参与血小板的凋亡。 展开更多
关键词 hsa-miR-326 双荧光素酶报告基因 bcl2l1 BAK1
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Network pharmacology and molecular docking identify mechanisms of medicinal plant-derived 1,2,3,4,6-penta-O-galloyl-beta-D-glucose treating gastric cancer
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作者 MAN REN YUAN YANG +3 位作者 DAN LI NANNAN ZHAO YUPING WANG YONGNING ZHOU 《BIOCELL》 SCIE 2023年第5期977-989,共13页
Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against ... Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against gastric cancer were explored through network pharmacology and molecular docking.First,the targets of PGG were searched in the Herbal Ingredients’Targets(HIT),Similarity Ensemble Approach(SEA),and Super-PRED databases.The potential targets related to gastric cancer were predicted from the Human Gene Database(GeneCards)and DisGeNET databases.The intersecting targets of PGG and gastric cancer were obtained by Venn diagram and then subjected to protein-protein interaction analysis to screen hub targets.Functional and pathway enrichment of hub targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases.The differential expression and survival analysis of hub targets in gastric cancer were performed based on The Cancer Genome Atlas database.Finally,the affinity of PGG with hub targets was visualized by molecular docking.Results:Three hub targets were screened,including mitogen-activated protein kinase 14(MAPK14),BCL2 like 1(BCL2L1),and vascular endothelial growth factor A(VEGFA).MAPK14 had a higher expression,while BCL2L1 and VEGFA had lower expression in gastric cancer than in normal conditions.Enrichment analysis indicated enrichment of these hub targets in MAPK,neurotrophin,programmed death-ligand 1(PD-L1)checkpoint,phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt),Ras,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Conclusion:Therefore,network pharmacology and molecular docking analyses revealed that PGG exerts a therapeutic efficacy on gastric cancer by multiple targets(MAPK14,BCL2L1,and VEGFA)and pathways(MAPK,PD-L1 checkpoint,PI3K-Akt,Ras,and HIF-1 pathways). 展开更多
关键词 1 2 3 4 6-penta-O-galloyl-beta-D-glucose Gastric cancer Network pharmacology Molecular docking MAPK14 bcl2l1 VEGFA
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Bcl-2、PD-L1在大肠癌组织中的表达及意义 被引量:5
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作者 张美云 杨永岩 +1 位作者 王新花 李晓凤 《四川大学学报(医学版)》 CAS CSCD 北大核心 2012年第6期827-829,859,共4页
目的探讨结肠癌组织中凋亡抑制基因Bcl-2蛋白、免疫共刺激分子PD-L1蛋白的表达及其与肿瘤转移的关系。方法应用免疫组化技术检测57例新鲜大肠癌组织及其癌旁正常组织中Bcl-2、PD-L1的表达,分析Bcl-2、PD-L1表达与大肠癌患者临床病理特... 目的探讨结肠癌组织中凋亡抑制基因Bcl-2蛋白、免疫共刺激分子PD-L1蛋白的表达及其与肿瘤转移的关系。方法应用免疫组化技术检测57例新鲜大肠癌组织及其癌旁正常组织中Bcl-2、PD-L1的表达,分析Bcl-2、PD-L1表达与大肠癌患者临床病理特征的关系。结果大肠癌组织中Bcl-2蛋白阳性表达率为75.43%,而癌旁正常组织中阳性表达率为52.63%,两者差异具有统计学意义(P<0.05);大肠癌组织中有PD-L1蛋白的原位表达,阳性表达率为45.61%,而癌旁正常组织PD-L1蛋白阳性表达率为15.79%,两者差异具有统计学意义(P<0.01);Bcl-2的表达率和表达强度与病理学分化程度有关,高-中分化大肠癌患者癌组织中Bcl-2的表达率和表达强度高于低分化者,差异有统计学意义(P<0.05);PD-L1蛋白的阳性表达率与大肠癌的淋巴结转移有关(P<0.05),而与浸润深度无关。在高-中分化组、Dukes分期A+B组、无淋巴结转移组中Bcl-2的阳性表达率高于PD-L1(P<0.05),而在低分化组、Dukes分期C+D组、有淋巴结转移组中二者表达率无明显差异(P>0.05)。结论 Bcl-2可能与结肠癌的病理学分化程度有关,PD-L1可能与结肠癌的转移发展有关;共检测Bcl-2和PD-L1可能预测大肠癌的病理分化程度、Dukes分期及有无淋巴结转移。 展开更多
关键词 bcl-2 PD-l1 大肠癌 临床病理 淋巴结转移
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Anti-apoptotic protein BCL-XL as a therapeutic vulnerability in gastric cancer
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作者 Yumin Wei Liping Zhang +9 位作者 Chao Wang Zefeng Li Mingjie Luo Guomin Xie Xingjiu Yang Mengyuan Li Shuyue Ren Dongbing Zhao Ran Gao Jia-Nan Gong 《Animal Models and Experimental Medicine》 CAS CSCD 2023年第3期245-254,共10页
Background: New therapeutic targets are needed to improve the outcomes for gastric cancer(GC) patients with advanced disease. Evasion of programmed cell death(apoptosis) is a hallmark of cancer cells and direct induct... Background: New therapeutic targets are needed to improve the outcomes for gastric cancer(GC) patients with advanced disease. Evasion of programmed cell death(apoptosis) is a hallmark of cancer cells and direct induction of apoptosis by targeting the pro-survival BCL2 family proteins represents a promising therapeutic strategy for cancer treatment. Therefore, understanding the molecular mechanisms underpinning cancer cell survival could provide a molecular basis for potential therapeutic interventions. Method: Here we explored the role of BCL2L1 and the encoded anti-apoptotic BCL-XL in GC. Using Droplet Digital PCR(ddPCR) technology to investigate the DNA amplification of BCL2L1 in GC samples and GC cell lines, the sensitivity of GC cell lines to selective BCL-XL inhibitors A1155463 and A1331852, pan-inhibitor ABT-263, and VHL-based PROTAC-BCL-XL was analyzed using(CellTiter-Glo) CTG assay in vitro. Western Blot(WB) was used to detect the protein expression of BCL2 family members in GC cell lines and the manner in which PROTAC-BCL-XL kills GC cells. Coimmunoprecipitation(Co-IP) was used to investigate the mechanism of A1331852 and ABT-263 kills GC cell lines. DDPCR, WB, and real-time PCR(RTPCR) were used to investigate the correlation between DNA, RNA, protein levels, and drug activity. Results: The functional assay showed that a subset of GC cell lines relies on BCL-XL for survival. In gastric cancer cell lines, BCL-XL inhibitors A1155463 and A1331852 are more sensitive than the pan BCL2 family inhibitor ABT-263, indicating that ABT-263 is not an optimal inhibitor of BCL-XL. VHL-based PROTAC-BCL-XL DT2216 appears to be active in GC cells. DT2216 induces apoptosis of gastric cancer cells in a time-and dose-dependent manner through the proteasome pathway. Statistical analysis showed that the BCL-XL protein level predicts the response of GC cells to BCL-XL targeting therapy and BCL2L1 gene CNVs do not reliably predict BCL-XL expression.Conclusion: We identified BCL-XL as a promising therapeutic target in a subset o 展开更多
关键词 apoptosis bcl2l1(bcl-Xl) gastric cancer(GC) PROTAC-bcl-Xl selective bcl-Xl inhibitors
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Bcl-2和PD-L1在大肠癌组织中的表达及两者与大肠癌侵袭转移的相关性 被引量:2
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作者 李晓凤 巴彩霞 +2 位作者 高辉 张美云 白雪峰 《癌症进展》 2011年第6期725-729,共5页
目的分析Bcl-2及PD-L1在大肠癌中的表达并探讨其与大肠癌临床病理特征之间的关系,及与大肠癌侵袭转移的相关性。方法用免疫组化法检测57例手术切除大肠癌组织新鲜标本及癌旁正常黏膜组织中Bcl-2及PD-L1的表达,并结合临床病理特征进行相... 目的分析Bcl-2及PD-L1在大肠癌中的表达并探讨其与大肠癌临床病理特征之间的关系,及与大肠癌侵袭转移的相关性。方法用免疫组化法检测57例手术切除大肠癌组织新鲜标本及癌旁正常黏膜组织中Bcl-2及PD-L1的表达,并结合临床病理特征进行相关性分析。结果①与癌旁正常组织相比,Bcl-2及PD-L1在大肠癌组织中的表达明显升高,有统计学差异(P<0.05)。②Bcl-2及PD-L1在大肠癌患者中高-中分化组与低分化组相比,表达明显升高,有显著性差异(P<0.01);PD-L1在大肠癌患者中有淋巴结转移组(Dukes分期C+D)与无淋巴结转移组(Dukes分期A+B)相比,表达升高,有统计学差异(P<0.05)。③在高-中分化的大肠癌组织中,PD-L1阴性组中Bcl-2阳性表达明显高于PD-L1阳性组,有显著统计学差异(P<0.01)。结论联合检测大肠癌组织中Bcl-2与PD-L1的表达,能协助判断大肠癌侵袭转移的能力,对大肠癌的诊断、指导治疗及评价预后有重要的临床意义。 展开更多
关键词 bcl-2 PD-l1 大肠癌 病理分期 淋巴结转移
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