DZNep对裸鼠食管鳞癌移植瘤生长的抑制作用
Inhibition effects of DZNep on growth of esophageal squamous cell carcinoma xenograft in nude mice

目的:探讨EZH2抑制剂DZNep对裸鼠Eca109细胞移植瘤生长及mTOR/p70S6K信号通路的影响。方法:将Eca109细胞接种于15只裸鼠右侧背部皮下构建裸鼠移植瘤模型后分为3组,每组5只,其中2组分别腹腔注射5-氟尿嘧啶(5-FU)、DZNep治疗2周,另外1组腹腔注射生理盐水作为对照组。观察肿瘤生长情况,采用Western blot检测肿瘤组织中EZH2、SAHH、组蛋白甲基化相关蛋白及mTOR/p70S6K信号通路相关蛋白、Caspase-3、E-cadherin的表达情况,并通过TUNEL法检测肿瘤组织中细胞的凋亡,计算细胞凋亡率。结果:DZNep组肿瘤块质量小于对照组(P<0.05)。与对照组比较,DZNep组肿瘤组织中Caspase-3和E-cadherin表达水平增高,细胞凋亡率升高(P<0.05)。另外,与对照组相比,DZNep组H3K27me3表达降低,PTEN表达升高,mTOR和p-p70S6K表达均下降(P<0.05)。结论:DZNep可抑制食管鳞癌移植瘤增长,并诱导肿瘤细胞凋亡; 其机制可能是通过对EZH2的抑制增强PTEN的表达,从而抑制mTOR/p70S6K信号通路的激活。
Aim: To observe the effects of DZNep on the growth of esophageal squamous cell carcinoma(ESCC)xenograft and mTOR/p70S6K signaling pathway in vivo.Methods: Eca109 cells were injected into 15 nude mice to establish Eca109 cell xenograft mouse model. These 15 mice were randomly allocated into 3 groups. Mice in one group were intra-peritoneally injected with 5-FU every other day for 2 weeks, mice in one group were injected with DZNep, and mice in the last group were injected with normal saline as control. Then, Western blot was employed to detect the expressions of EZH2, SAHH, histone methylation related protein, mTOR/p70S6K signal pathway related protein, Caspase-3, and E-cadherin in tumor tissue. And TUNEL was used to detect the cell apoptosis in tumor.Results: The tumor weight was decreased significantly in DZNep group compared with that in control group(P<0.05). Meanwhile, the expression of Caspase-3 and E-cadherin and the apoptosis rate were increased significantly in tumor tissue of DZNep group(P<0.05). The expression of PTEN was increased, and the expressions of H3K27me3, mTOR and phosphorylated p70S6K were decreased in DZNep group(P<0.05).Conclusion: DZNep could inhibit ESCC xenograft growth and promote ESCC cell apoptosis in vivo, by inhibiting the activation of mTOR/p70S6K signal pathway