阿司匹林逆转肝癌上皮细胞间质化改变的实验研究

The experimental study on aspirin inverting EMT in hepatocellular carcinoma

目的探讨阿司匹林能否抑制肝癌增殖过程中发生的上皮细胞间质化改变。方法构建12只裸鼠人肝癌原位生长模型,平均分为实验组和对照组。实验组连续5周灌胃阿司匹林(0.3g/kg),对照组灌胃等量生理盐水,治疗结束后取肺脏和肝脏,连续切片检测2组肺转移结节数目,免疫组化检测2组肝癌组织中上皮细胞间质化改变(EMT)相关标志物E-cadherin、vimentin及N-cadherin的表达。结果阿司匹林治疗后肝癌大小无明显变化,而肺转移结节数却明显降低,即对照组(26.33±5.43)个与治疗组(11.43±2.56)个,差异有统计学意义(P=0.0161),且E-cadherin在阿司匹林治疗后的肝癌组织中表达明显增加(P=0.0116),而代表间质特点的Vi-mentin和N-cadherin则在阿司匹林治疗后表达明显降低。结论阿司匹林能够抑制肝癌发生上皮细胞间质化改变,减少肺转移的发生。

Objective To explore whether aspirin could invert EMT occurred in the process of HCC proliferation. Methods Twelve orthotopic nude mouse models were established and then aspirin were gavaged for 5 weeks to explore the effect on pul-monary metastasis, and the control group was used saline instead. The pulmonary metastasis was evaluated by continuous pulmonary tis- sue sections and HE stains. The biomarkers such as E - cadherin, vimentin and N - cadherin were evaluated by immunohistochemical stains. Results Although there was no significant difference in hepatocellular carcinoma size after aspirin treatment, the significantly re-duced number of pulmonary nodules were observed between control group and aspirin group （P = 0. 016 1 ）. The expression of increased E - cadherin （ P = 0.011 6） and decreased N - eadherin （ P = 0. 023 8 ） and vimentin （ P = 0. 004 4 ） were also observed after aspirin treatment. Conclusion Aspirin can inverse the occurrence of EMT in hepatocellular carcinoma and reduce the pulmonary metastasis.