目的:研究熊果酸(Ursolic acid, UA)对荷肺癌裸小鼠移植瘤生长的影响并探讨其机制.方法:通过右侧腹股沟区皮下接种人非小细胞肺癌A549细胞的方法建立荷肺癌裸小鼠模型,分别腹腔注射给予不同剂量UA(5、10、20 mg/(kg·d))和顺铂(2 mg/(kg·d))进行干预治疗,疗程14d.观察裸小鼠生存状态和肿瘤特征;称量瘤重并计算抑瘤率;HE染色法观察肿瘤组织形态结构改变,TUNEL染色法观察肿瘤组织细胞凋亡状况,IHC法检测肿瘤组织中Caspase-3、Bax、bcl-2蛋白表达并进行半定量分析.结果:与模型组比较发现:经UA治疗14 d能够明显改善荷肺癌裸小鼠饮食状况和精神状态,瘤体减小、活动度和硬度降低;较模型组,UA治疗组移植瘤组织呈现细胞皱缩、片状坏死等病变,凋亡细胞数量显著增多,瘤体重量显著减轻、抑瘤率显著升高;移植瘤组织中Caspase-3蛋白和Bax蛋白表达显著升高、bcl-2蛋白表达显著降低,Bax/bcl-2比值显著升高;UA上述作用均具有一定的剂量依赖性.结论:UA具有抑制荷肺癌裸小鼠移植瘤生长的作用,作用机制可能与UA调节凋亡相关蛋白(Caspase-3、Bax、bcl-2)表达而促进肿瘤细胞凋亡有关.%Objective:To investigate the inhibitive effects and mechanism of Ursolic Acid (UA) on xenografts growth in lung cancer of nude mice.Methods :The nude mice models bearing lung cancer were made by injecting inoculation human lung cell line A549 were treated with UA(5, 10, 20 mg/(kg·d)) and Cisplatin 2 mg/(kg·d) for 14d.The nude mice general states and tumor growth conditions were observed, the histopathological changes of tumor tissue was observed by HE staining;the tumor cells apoptosis was detected by TUNEL staining;the expression of Caspase-3, Bax,bcl-2 protein were detected by immunohistochemistry (IHC).Results:The nude mice bearing lung cancer were treated with UA for 14 d appeared food situation mental condition were improved, tumor was reduced, activity and hardness were poorer;necrosis presentation, tumor cell shrinkage and other pathological morphological changes appeared, the number of apoptotic cells in tumor tissue was significantly increased;the tumor weight of UA treated groups were significantly decreased and the inhibition rate were significantly increased;the expression of Bax and Caspase-3 were significantly increased, the expression of bcl-2 protein was significantly decreased, and the ratio of Bax/bcl-2 were significantly increased, all of the effects of UA above were dose-dependent with a certain.Conclusion:UA has inhibitive effects on xenografts growth in lung cancer of nude mice, which perhaps related to its effects of regulating the expression of apoptosis-related proteins (Caspase-3, Bax, bcl-2) to promoting tumor cell apoptosis.
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