夜香树甾体皂苷抑制人肝癌裸鼠移植瘤的研究

目的: 观察夜香树甾体皂苷(SSCN)对HepG2肝癌移植瘤的抑制作用,并探讨其抑瘤的可能机制。方法: 从夜香树叶和嫩枝用有机溶剂提取、分离并鉴定SSCN。应用人肝癌细胞株HepG2皮下接种法建立移植瘤模型,建模成功后将荷人肝癌裸鼠随机分为5组:生理盐水组0.2 mL·次^-1、沙利度胺(TLD)组200 mg·kg^-1和SSCN低,中,高剂量组4,6,8 mg·kg^-1。隔天ip给药,在治疗期间测量皮下移植瘤的长径和短径;30 d后处死裸鼠,免疫组化法检测移植瘤中微血管密度(MVD)和血管内皮细胞生长因子(VEGF)的表达,用酶联免疫法(ELISA)法检测裸鼠血清中白细胞介素-8(IL-8)的表达。结果: SSCN低,中,高剂量ip给药对肝癌裸鼠移植瘤相对肿瘤细胞增殖率分别为对照组(100%)的48.26%,42.94%,41.57%,TLD组的相对肿瘤增殖率为42.19%。SSCN各组及TLD组的MVD,VEGF和IL-8的水平都明显低于模型组(P<0.01)。结论: 夜香树叶甾体皂苷体内对BALB/c裸鼠肝癌移植瘤有一定的抑制作用,其作用机制可能通过抑制VEGF,MVD的表达以及IL-8的转录,导致肿瘤血管生成受到抑制。

Antitumor Effects of Steroidal Saponins of Cestrum nocturnum (SSCN) on Human Hepatocellular Carcinoma Xenografts in Nude Mice

Objective: To investigate the antitumor effects and mechanism of steroidal saponins of Cestrum nocturnum(SSCN) on human hepatocellular carcinoma xenografts in nude mice in vivo. Method: SSCN from the leaves and twigs of cestrum nocturnum,Linn were separated and their structures were identified by solvent;the animal model of human hepatocellular carcinoma xenografts was constructed by subcutaneous inoculation of hepatocellular carcinoma HepG2 cells into nude mice.The mice were randomly divided into five groups:NS group(0.2 mL),thalidomide(TLD) group(200 mg·kg^-1),and SSCN low,medium and high dose groups(4,6,8 mg·kg^-1).During treatment,tumor size was measured.The mice were killed 30 days later to observe tumor morphology.The angiogenesis was assessed by immunohistochemical staining using anti-vascular endothelia grouth factor(VEGF) and cluster of differentiation 34(CD34) antibodies,the expression of interleukin-8(IL-8) of serum was detected by ELISA. Result: The relative proliferation rate in experimental groups (low,medium and high doses) was 48.26%,42.94% and 41.57%,respectively,and in positive group (thalidomide) the relative proliferation rate was 42.19%. Compared with the NS group, the expression of MVD, VEGF and IL-8 were was markedly lowered in all SSCN treatment groups and TLD group (P<0.01). Conclusion: SSCN has a certain inhibitory effect on tumor nude mice in vivo. The anti-tumor mechanism is probably related to the inhibition of activity of VEGF, MVD and IL-8, and downregulating the expression of proangiogenic factors.