【摘要】 目的研究熊果酸(UA)对荷肺癌裸小鼠移植瘤生长的抑制作用及其机制。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,将造模成功小鼠随机分为模型组、UA 5 mg/(kg·d)组、UA 10 mg/(kg·d)组、UA 20 mg/(kg·d)组和顺铂2 mg/(kg·d)组,每组12只,各给药组分别腹腔注射相应剂量的药物,模型组腹腔注射等量生理盐水,均1次/d,连续14 d。干预结束后,观察各组裸小鼠生存状态和肿瘤特征;颈椎脱臼处死动物后剥取肿瘤组织,称质量并计算抑瘤率;HE染色法观察肿瘤组织形态结构,TUNEL染色法观察肿瘤组织细胞凋亡情况,IHC法检测肿瘤组织中Caspase-3、Bax、Bcl-2蛋白表达情况并进行半定量分析。结果与模型组比较,各给药组小鼠精神状态、饮食情况均明显改善,移植瘤组织瘤体较小、活动度和硬度均较低,移植瘤组织细胞不同程度皱缩、数量减少、间隙增大以及片状坏死等,移植瘤组织细胞凋亡数量明显增多,其中UA 20 mg/(kg·d)组改善情况最为显著。UA 10 mg/(kg·d)组、UA 20 mg/(kg·d)组和顺铂组小鼠移植瘤瘤体质量和Bcl-2蛋白表达OD值均显著低于模型组(P均<0.05),各给药组抑瘤率和移植瘤组织中Caspase-3和Bax蛋白表达OD值及Bax/Bcl-2比值均明显高于模型组(P均<0.05);UA 20 mg/(kg·d)组瘤体质量、抑瘤率、Bcl-2和Bax蛋白表达OD值与顺铂组比较差异均无统计学意义(P均>0.05),Caspase-3蛋白表达OD值及Bax/Bcl-2比值均显著高于顺铂组(P均<0.05)。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。更多还原

【Abstract】 Objective It is to investigate the inhibiting effects of ursolic acid( UA) on xenografts growth in nude mice with lung cancer. Methods The nude mice models with lung cancer were made by inoculation of human lung cell line A549 in their right inguinal region,the successful models were randomly divided into model group,5 mg/( kg·d) UA group,10 mg/( kg·d) group and 20 mg/( kg·d) group,2 mg/( kg·d) cisplatin group,each group had 12 mice and were treated with respective medicine by intraperitoneal injection once per day for 14 days,the model group was given the same dose of normal saline.After treatment,the general states and tumor growth conditions of all the mice were observed in every group. 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 Compared with the mice in model group,food situation and mental condition were improved,tumor was reduced,activity and hardness were poorer,necrosis presentation,tumor cell shrinkage and other pathological morphological changes could be found in every treatment group,furthermore,the number of apoptotic cells in tumor tissue was significantly increased,and the improvements in 20 mg/( kg·d) group were the best. The tumor weight and OD value of Bcl-2 expression in 10 mg/( kg·d) group and 20 mg/( kg·d)group,2 mg/( kg·d) cisplatin group were significantly lower while the inhibition rate,OD value of the expression of Bax and Caspase-3 and the ratio of Bax/Bcl-2 in tumor tissue were significantly higher than that in model group( P < 0. 05). The OD value of Caspase-3 expression and ratio of Bax/Bcl-2 in 20 mg/( kg·d) UA group was higher than that in cisplatin group( P <0. 05),but no significant difference in tumor weight,inhibiting rate of tumor,and OD value of Bcl-2 and Bax expression was found in the two groups( P > 0. 05). Conclusion UA has inhibitive effects on xenografts growth in nude mice with lung cancer,which perhaps related to its effects of regulating the expression of apoptosis-related proteins( Caspase-3,Bax,Bcl-2) to promoting tumor cell apoptosis.更多还原