The Antitumor Effect of Gekko Sulfated Glycopeptide by Inhibiting bFGF-Induced Lymphangiogenesis.
The Antitumor Effect of Gekko Sulfated Glycopeptide by Inhibiting bFGF-Induced Lymphangiogenesis.
复制标题
Gekko 硫酸化糖肽通过抑制 bFGF 诱导的淋巴管生成发挥抗肿瘤作用
DOI：
10.1155/2016/7396392
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发表时间：
2016
影响因子：
--
通讯作者：
Wu XZ
中科院分区：
文献类型：
--
作者：
Ding XL;Man YN;Hao J;Zhu CH;Liu C;Yang X;Wu XZ
Objective.研究壁虎硫酸糖肽（GSPP）对人淋巴管内皮细胞（hLECs）的抗淋巴管生成作用。方法.用MTS法检测GSPP对hLECs增殖的抑制作用，流式细胞仪检测细胞周期分布，创伤愈合实验和transwell实验检测GSPP对hLECs迁移的抑制作用，试管形成实验检测GSPP对淋巴管生成的抑制作用，MTT法检测GSPP对hLECs增殖的抑制作用，MTT法检测GSPP对hLECs增殖的抑制作用，流式细胞仪检测GSPP对hLECs增殖的抑制作用，MTT法检测GSPP对hLECs增殖的抑制作用。Western blotting检测GSPP和碱性成纤维细胞生长因子（bFGF）作用后细胞外信号调节激酶1/2（Erk 1/2）和p-Erk 1/2的表达。建立裸鼠体内抗肿瘤模型，研究GSPP的体内抗肿瘤作用。通过免疫组化染色证实GSPP在体内引起的淋巴管生成减少。结果GSPP（10 μg/mL、100 μg/mL）可显著抑制bFGF诱导的hLEC增殖、迁移和管样结构形成（P < 0.05），并对抗bFGF诱导的Erk 1/2磷酸化激活。在体内，GSPP（200 mg/kg/d）不仅抑制结肠癌的生长，而且抑制肿瘤淋巴管生成。结论GSPP通过抑制bFGF诱导的淋巴管生成而具有抗肿瘤作用，并可能进一步抑制肿瘤淋巴道转移。
Objective. To study the antilymphangiogenesis effect of Gekko Sulfated Glycopeptide (GSPP) on human lymphatic endothelial cells (hLECs). Methods. MTS was conducted to confirm the antiproliferation effect of GSPP on hLECs; flow cytometry was employed to detect hLECs cycle distribution; the antimigration effect of GSPP on hLECs was investigated by wound healing experiment and transwell experiment; tube formation assay was used to examine its inhibitory effect on the lymphangiogenesis; western blotting was conducted to detect the expression of extracellular signal-regulated kinase1/2 (Erk1/2) and p-Erk1/2 after GSPP and basic fibroblast growth factor (bFGF) treatment. Nude mice models were established to investigate the antitumor effect of GSPP in vivo. Decreased lymphangiogenesis caused by GSPP in vivo was verified by immunohistochemical staining. Results. In vitro, GSPP (10 μg/mL, 100 μg/mL) significantly inhibited bFGF-induced hLECs proliferation, migration, and tube-like structure formation (P < 0.05) and antagonized the phosphorylation activation of Erk1/2 induced by bFGF. In vivo, GSPP treatment (200 mg/kg/d) not only inhibited the growth of colon carcinoma, but also inhibited the tumor lymphangiogenesis. Conclusion. GSPP possesses the antitumor ability by inhibiting bFGF-inducing lymphangiogenesis in vitro and in vivo, which may further inhibit tumor lymphatic metastasis.