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Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma

机译:甘草甜素对肺腺癌小鼠模型的影响

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>Background: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2) in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. Methods: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TP?±). The animal model was confirmed by the hematoxylin and eosin (H&E) method. Tumor-bearing mice were then administered graded concentrations of glycyrrhizin, cisplatin or both. After the treatments, body weights of all animals were recorded, and immunohistochemistry staining of lung tissues and serum biochemistry detection of aspartate amino transferase (AST), alanine amino transferase (ALT), urea and creatinine were carried out. Results: Treatment with glycyrrhizin alone or the combination of cisplatin and glycyrrhizin profoundly reduced expression of thromboxane synthase (TxAS) as well as proliferating cell nuclear antigen (PCNA), recovered the body weight, and rescued damage of liver and kidney in tumor-bearing mice. Although it inhibited PCNA expression, cisplatin could not significantly suppress TxAS expression. Because of a positive feedback loop between TP?± and TxAS, the effects of glycyrrhizin are possibly attributable to the suppression of the TxA2 pathway. Conclusions: This study provides in vivo evidence to support glycyrrhizin as a potential candidate for developing new regimens to overcome tumor progression and the resistance and toxicity of cisplatin.
机译:> 背景: 当前,全球正在尝试确定潜在的低毒性抗癌药。先前的研究发现,甘草甜素通过抑制肺癌细胞系中的血栓烷A2(TxA2)发挥抗癌作用,且毒性低。然而,尚未在肺癌的动物模型中确定这些作用。 方法: 通过引入具有稳定转染TxA2受体(TP?±)的A549细胞,在裸鼠中建立人肺腺癌异种移植物。通过苏木精和曙红(H&E)方法确认了动物模型。然后给荷瘤小鼠施用分级浓度的甘草甜素,顺铂或两者。处理后,记录所有动物的体重,并对肺组织进行免疫组织化学染色,并进行天冬氨酸氨基转移酶(AST),丙氨酸氨基转移酶(ALT),尿素和肌酐的血清生化检测。 结果: 单独使用甘草甜素或顺铂和甘草甜素的联合治疗可大大降低血栓烷合酶(TxAS)和增殖细胞核抗原(PCNA)的表达,从而恢复了机体体重,并挽救了荷瘤小鼠的肝脏和肾脏。尽管顺铂抑制PCNA的表达,但它不能显着抑制TxAS的表达。由于TPα±和TxAS之间存在正反馈回路,因此,甘草甜素的作用可能归因于TxA2途径的抑制。 结论: 该研究提供了体内证据,支持甘草甜素作为开发新方案以克服肿瘤进展以及抗药性和耐药性的潜在候选者。顺铂。

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