番茄红素对荷肝癌裸小鼠移植瘤生长的作用及机制研究

目的研究番茄红素(Lycopene,LP)对荷肝癌裸小鼠移植瘤生长的影响及其机制。方法通过背部皮下注射接种肝癌Hep G2细胞的方法建立荷肝癌裸小鼠模型,并分别腹腔注射5、10、20 mg/(kg·d)的LP和2 mg/(kg·d)的顺铂进行干预治疗,疗程为14 d。治疗后,观察各组裸小鼠的一般生存状态及肿瘤生长状况,称取瘤体质量并计算抑瘤率;通过苏木精-尹红(HE)染色观察肿瘤组织形态结构改变,末端标记法(TUNEL)检测肿瘤组织细胞凋亡状况,免疫组织化学法(IHC)观察肿瘤组织凋亡相关蛋白(caspase-3、Bax、bcl-2)表达。结果经LP治疗14 d,荷肝癌裸小鼠饮食状况和精神状态明显改善,瘤体减小,活动度和硬度降低,肿瘤组织呈现细胞皱缩、片状坏死等病理性改变,凋亡细胞数量明显增多;瘤体质量显著减轻、抑瘤率显著升高;肿瘤组织中caspase-3和Bax表达显著上调,而bcl-2显著下调,Bax/bcl-2比值显著升高;LP上述作用均具有一定的剂量依赖性。结论番茄红素对荷肝癌裸小鼠移植瘤生长具有一定的抑制作用,其机制可能与番茄红素调节凋亡相关基因蛋白表达而促进肿瘤组织细胞凋亡有关。

Effects and mechanism of lycopene on xenografts growth in liver cancer of nude mice

Objective To investigate the effects of Lycopene (LP) on xenografts growth in liver cancer of nude mice.Methods The nude mice models bearing liver cancer were made by injecting inoculation human liver cell line HepG2 and were treated with 5,10 and 20 mg/(kg·d) of LP and 2 mg/(kg·d) of cisplatin for 14 d.The rats' general states and tumor growth conditions were observed,and the histopathological change of tumor tissue was observed by HE staining.The tumor cells apoptosis was detected by TUNEL.The expression of caspase-3,Bax and bcl-2 protein was detected by immunohistochemistry (IHC).Results The food and mental condition was improved after nude mice bearing liver cancer was treated with LP for 14 d,the tumor was reduced,and the activity and hardness was decreased.There were necrosis presentation,tumor cell shrinkage and other pathological morphological changes that appeared,and the number of apoptotic cells in tumor tissue was increased.The tumor weights of LP groups were decreased and the inhibition rates were increased.The expression of caspase-3 and Bax was significantly increased,while the expression of bcl-2 protein was decreased,and the ratio of Bax/bcl-2 was significantly increased;all the above effects were dose-dependent.Conclusion LP has inhibitive effects on xenografts growth in liver cancer of nude mice,which is perhaps related to its effects of regulating the expression of apoptosis-related genes and protein to promote tumor cell apoptosis.