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The PPARγ Agonist Rosiglitazone Enhances the Radiosensitivity of Human Pancreatic Cancer Cells

机译:PPARγ激动剂Rosiglitazone提高人胰腺癌细胞的放射敏感性

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Purpose: As radiation therapy is widely used for the management of pancreatic cancer, identifying novel targets to improve the radiosensitivity of cancer cells is beneficial. Rosiglitazone, a specific peroxisome proliferator-activated receptor γ (PPARγ) agonist, has an inhibitory effect on various types of cancer cells. The purpose of this paper is to investigate the effect of rosiglitazone on the radiosensitivity of pancreatic cancer cells and the potential mechanism. Materials and Methods: PPARγ expression in pancreatic cancer and adjacent tissues was evaluated using immunohistochemistry analysis. The viability, migration and invasion ability of PANC1 and PaTu8988 cells were detected using MTT assay, scratch-wound assay and transwell invasion assay. The effect of rosiglitazone on radiosensitivity of the cells was determined using the clonogenic assay. PANC1 cells were inoculated into BALB/c mice to establish tumors. Microarray was used to investigate changes of genes involved. Results: Higher PPARγ expression was demonstrated in pancreatic cancer tissues compared with para-carcinoma tissues. Rosiglitazone inhibited the cell viability and enhanced the radiation-induced anti-migration and anti-invasion effect. Rosiglitazone potentiated the radiosensitivity of pancreatic cancer cells and PANC1 xenografts. Microarray analysis revealed that rosiglitazone plus radiation altered the expression of multiple genes and affected multiple pathways. Conclusion: Rosiglitazone enhances the radiosensitivity of human pancreatic cancer cells in vitro and in vivo via complex mechanisms.
机译:目的:由于放射治疗广泛用于胰腺癌的管理,鉴定新的靶标以提高癌细胞的放射敏感性是有益的。 Rosiglitazone是一种特异的过氧化物体增殖物激活受体γ(PPARγ)激动剂,对各种类型的癌细胞具有抑制作用。本文的目的是研究罗格列酮对胰腺癌细胞辐射敏感性的影响及潜在机制。材料和方法:使用免疫组化分析评估胰腺癌和相邻组织中的PPARγ表达。使用MTT测定法检测PANC1和PATU8988细胞的可行性,迁移和侵袭能力,刮伤伤口测定和Transwell侵袭测定。利用克隆核测定法测定Rosiglitazone对细胞放射敏感性的影响。将Panc1细胞接种到Balb / c小鼠中以建立肿瘤。微阵列用于研究所涉及基因的变化。结果:与对癌组织相比,在胰腺癌组织中证明了较高的PPARγ表达。 Rosiglitazone抑制细胞活力并增强了辐射诱导的抗迁移和抗侵袭效应。 Rosiglitazone强调了胰腺癌细胞和Panc1异种移植物的放射敏感性。微阵列分析显示,Rosiglitazone Plus辐射改变了多种基因的表达并影响了多种途径。结论:Rosiglitazone通过复杂机制在体外和体内体内增强人胰腺癌细胞的放射敏感性。

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