Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma
Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma
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DOI：
10.1159/000467897
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Huang, Run-Yue
中科院分区：
文献类型：
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作者：
Deng, Qing-Ping;Wang, Mao-Jie;Huang, Run-Yue
背景：目前，全球都在努力寻找潜在的低毒性抗癌药物。以往的研究发现，在肺癌细胞株中，黄嘌呤通过抑制血栓素A2（TxA 2）发挥低毒性的抗癌作用。然而，这些影响尚未在肺癌动物模型中确定。研究方法：通过引入具有TxA 2受体（TP α）的稳定转染的A549细胞在裸鼠中建立人肺腺癌异种移植物。通过苏木精-伊红（H&E）法证实动物模型。然后对荷瘤小鼠给予分级浓度的甘草酸、顺铂或两者。给药后，记录各组动物体重，行肺组织免疫组化染色及血清天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、尿素、肌酐生化检测。结果如下：单独或联合顺铂和顺铂治疗显著降低了血栓素合酶（TxAS）和增殖细胞核抗原（PCNA）的表达，恢复了荷瘤小鼠的体重，并挽救了荷瘤小鼠的肝和肾损伤。顺铂虽然抑制PCNA的表达，但不能显著抑制TxAS的表达。由于TP α和TxAS之间存在正反馈环，因此，Bisocin的作用可能归因于TxA 2通路的抑制。结论：这项研究提供了体内证据，以支持作为一个潜在的候选人，开发新的方案，以克服肿瘤的进展和耐药性和顺铂的毒性。(C)2017作者由S.发布Karger AG，巴塞尔
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 alpha). 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 alpha 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. (C) 2017 The Author(s) Published by S. Karger AG, Basel