新生血管特异性结合肽GX1二聚体抑制胃癌新生血管生成的实验研究

目的:探讨新生血管特异性结合肽GX1二聚体对胃癌新生血管生成的影响。方法:化学合成GX1二聚体、GX1单体、对照肽二聚体，CCK-8实验、管状结构形成实验、迁移实验研究GX1二聚体对胃癌血管内皮细胞（co-HUVEC）增殖、微管形成、迁移能力的影响，流式细胞学技术分析其对细胞周期分布和凋亡的影响。结果:CCK-8结果显示，GX1二聚体与对照肽二聚体及PBS对照组相比，100~200 μmol/L可抑制co-HUVEC增殖，具有统计学差异（P<0.05），并呈剂量依赖性，GX1二聚体较单体抑制作用增强，并有统计学差异（P<0.05）。管状结构形成实验、细胞损伤迁移实验结果显示，与对照肽二聚体及对照组PBS 相比，GX1二聚体及GX1单体，均可抑制胃癌内皮细胞管状结构的形成及迁移，且二聚体抑制作用强于单体；对照肽二聚体仅有轻微的抑制胃癌内皮细胞管状结构的形成及迁移。流式细胞术分析显示，与对照肽二聚体及PBS对照组相比，GX1二聚体及GX1单体均可诱导细胞凋亡（P<0.05），且GX1二聚体的诱导作用强于GX1单体（P<0.05），而对细胞周期分布则无明显影响。结论:GX1二聚体和GX1单体均可抑制胃癌新生血管内皮细胞增殖、微管形成、迁移能力及诱导凋亡，且GX1二聚体较GX1单体作用增强。GX1二聚体有望代替单体成为胃癌新生血管靶向治疗小肽类药物。

Neovasculature homing peptide dimeric GX1 showed antiangiogenesis to gastric cancer

Objective:To evaluate the antiangiogenesis ability of dimeric GX1 to gastric cancer angiogenesis.Methods:Dimeric GX1,GX1 monomer and dimeric control peptides were synthesized.Antiangiogenesis of dimeric GX1 on gastric cancer vasculature endothelial cells( co-HUVEC) was analyzed by CCK-8 assay,migration assay,and tube formation assay. Flow cytometry assay was performed to evaluate the effects of dimeric GX1 to co-HUVEC cycle and apoptosis. Results: CCK-8 assay showed that dimeric GX1,compared to both dimeric control peptides and PBS group,had significant inhibitory effect on the proliferation of co-HUVEC( P < 0. 05) from 100 to 200 μmol/L in dose-dependent manner. Dimeric GX1 showed more significant inhibitory effect than GX1 monomer( P < 0. 05).Tube formation assay and cell migration assay showed that both dimeric GX1 and GX1 monomer could inhibit tube formation and cell migration of co-HUVEC compared to dimeric control peptides and PBS group. Dimeric control peptides only showed slightly inhibitory effect on tube formation and cell migration of co-HUVEC. Flow cytometry assay also showed that both dimeric GX1 and GX1 monomer could induce co-HUVEC apoptosis compared to dimeric control peptides and PBS group( P < 0. 05),but dimeric GX1 had stronger induction effect than GX1 monomer( P <0. 05). In addition,there was no significant effect on cell cycle distribution. Conclusion: Dimeric GX1 owned more significant antiangiogenesis ability on co-HUVEC than GX1 monomer. Dimeric GX1 was more promising to be explored for effective antiangiogenesis targeting drug to gastric cancer.