Liu Minghua, Yang Sijin, Zhang Dan, Shui Pixian, Song Shanshan, Yao Jian, Dai Yong, Sun Qin
Department of Pharmacy, Luzhou Medical College Luzhou 646000, China.
Affiliated Hospital of Traditional Chinese Medicine, Luzhou Medical College Luzhou 646000, China.
Int J Clin Exp Med. 2014 Nov 15;7(11):3859-69. eCollection 2014.
To investigate whether fructopyrano-(1→4)-glucopyranose (FG) inhibits the proliferation of liver cancer cells and angiogenesis in a vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) dependent manner.
Bel-7402, HepG2 and SMMC-7721 cells with high expression of VEGF and VEGFR were screened. Bel-7402 cells and human microvascular endothelial cells (HMEC) were treated with FG for 48 h. CCK-8 assay was used to detect cell proliferation. Wound healing assay was used to investigate effect of FG on the migration of HMECs. Tube formation assay was done to test influence of FG on the angiogenesis of HMECs, and qRT-PCR and western blot assay were performed to detect mRNA and protein expression of VEGF, Fit-1 and KDR. Nude mice were inoculated with Bel-7402 cells, and influence of FG on tumor growth, microvessel density (MVD) and VEGF expression in tumor was investigated.
Bel-7402 cells had a significantly higher expression of VEGF and VEGFR when compared with HepG2 cells and SMMC-7721 cells. FG could markedly reduce the mRNA and protein expressions of VEGF, Fit-1 and KDR in Bel-7402 cells and inhibit the proliferation of Bel-7402 cells in a concentration dependent manner. In addition, FG was able to remarkably inhibit the proliferation, migration and angiogenesis of HMECs, exerting anti-angiogenetic effect. In cancer-bearing nude mice, FG was found to inhibit the tumor growth, reduce MVD in tumors and decrease the VEGF in tumors.
FG can inhibit proliferation of liver cancer cells and suppression angiogenesis in liver cancer in a VEGF/VEGFR dependent manner.
研究吡喃果糖基-(1→4)-吡喃葡萄糖（FG）是否以血管内皮生长因子（VEGF）/血管内皮生长因子受体（VEGFR）依赖的方式抑制肝癌细胞增殖和血管生成。
筛选出VEGF和VEGFR高表达的Bel-7402、HepG2和SMMC-7721细胞。用FG处理Bel-7402细胞和人微血管内皮细胞（HMEC）48小时。采用CCK-8法检测细胞增殖。采用划痕愈合试验研究FG对HMEC迁移的影响。进行管腔形成试验以检测FG对HMEC血管生成的影响，并进行qRT-PCR和蛋白质印迹试验以检测VEGF、Fit-1和KDR的mRNA和蛋白表达。将Bel-7402细胞接种于裸鼠，研究FG对肿瘤生长、肿瘤微血管密度（MVD）和肿瘤中VEGF表达的影响。
与HepG2细胞和SMMC-7721细胞相比，Bel-7402细胞中VEGF和VEGFR的表达明显更高。FG可显著降低Bel-7402细胞中VEGF、Fit-1和KDR的mRNA和蛋白表达，并以浓度依赖的方式抑制Bel-7402细胞的增殖。此外，FG能够显著抑制HMEC的增殖、迁移和血管生成，发挥抗血管生成作用。在荷瘤裸鼠中，发现FG可抑制肿瘤生长，降低肿瘤中的MVD并减少肿瘤中的VEGF。
FG可通过VEGF/VEGFR依赖的方式抑制肝癌细胞增殖并抑制肝癌血管生成。
