Meng Wenbo, Li Xun, Bai Zhongtian, Li Yan, Yuan Jinqiu, Liu Tao, Yan Jun, Zhou Wence, Zhu Kexiang, Zhang Hui, Li Yumin
The Second Hospital of Lanzhou University, Key Laboratory of Digestive System Tumors, Gansu Province, Lanzhou, Gansu Province, China ; Special Minimally Invasive Surgery, the First Hospital of Lanzhou University, Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, Gansu, China.
The Second Department of General Surgery, the First Hospital of Lanzhou University, Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, Gansu, China.
PLoS One. 2014 Feb 28;9(2):e90660. doi: 10.1371/journal.pone.0090660. eCollection 2014.
Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development.
甲胎蛋白不仅作为肝癌的诊断标志物,还具有多种生物学功能。然而,甲胎蛋白在肿瘤血管生成和细胞侵袭中的作用仍未完全明确。在本研究中,我们旨在评估甲胎蛋白是否能调节人肝癌细胞中的主要血管生成因子和基质金属蛋白酶。通过Stealth RNAi实现甲胎蛋白沉默。用全自动电化学发光免疫分析仪检测甲胎蛋白的表达。用蛋白质免疫印迹法和免疫细胞化学法检测血管内皮生长因子(VEGF)、血管内皮生长因子受体2(VEGFR-2)、基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶-2(MMP-2)的表达。用TUNEL法检测细胞凋亡。用体外血管生成检测试剂盒检测血管生成。甲胎蛋白沉默导致细胞凋亡增加,这与血管内皮生长因子、血管内皮生长因子受体2、基质金属蛋白酶-2/9的表达降低有关。这些结果表明,甲胎蛋白在肝癌发生发展过程中可能对血管生成和细胞侵袭起调节作用。