YC-1对人肝细胞癌裸鼠移植瘤的影响及其机制
Mechanism of Effects of YC-1 on Human Primary Hepatic Carcinoma Loaded in Nude Mice
-
摘要: 目的探讨缺氧诱导因子抑制剂(YC-1)对人肝癌细胞裸鼠皮下移植瘤的影响及其相关机制。方法用人肝癌细胞株SMMC-7721建立人肝癌裸鼠皮下移植瘤模型,待肿瘤生长至约(100~150)mm3时,将荷瘤裸鼠随机分为两组:实验组和对照组,分别给予YC-1和二甲基亚砜,观察两组裸鼠肿瘤生长情况;应用RT-PCR、Western blot及免疫组织化学方法检测移植瘤组织HIF-1α和VEGF表达。结果YC-1治疗组各时点肿瘤体积显著低于对照组(P<0. 05 );与对照组比较,实验组移植瘤组织HIF-1α mRNA表达差异无统计学意义(P>0.05),而HIF-1α蛋白的表达显著降低 (P<0. 05 );移植瘤组织VEGFmRNA及蛋白表达均显著低于对照组 (P<0. 05 )。结论YC-1可能通过下调HIF-1α和VEGF的表达来抑制肝癌的生长。Abstract: ObjectiveTo research the mechanism of effects of HIF-1α (YC-1) on implanted human primary hepatic carcinoma in nude mice. MethodsA total of 16 male nude mice were inoculated subcutaneously with 1 million SMMC-7721 cells. Once the tumor grew to (100~150)mm3, the mice were divided randomly into two groups and injected with YC-1 or DMSO respectively. Tumor size and weight were measured. Levels of HIF-1α and VEGF expressions in tumor tissue were detected by RT-PCR, Westetn blot or immunohistochemical respectively. ResultsTumors grew rapidly in the control group than those in the YC-1 treatment group. In YC-1 group therapy resulted in low expression of HIF-1α and VEGF than those in control groups(P<0.05). ConclusionYC-1 therapy was a promising approach to treat human liver cancer by suppression of HIF-1α and VEGF expression, which might contribute to inhibit tumor growth and angiogenesis.