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  

Neovasculature homing peptide dimeric GX1 showed antiangiogenesis to gastric cancer

作　　者：罗莹莹 刘惊涛 雷志杰 张海萍[1] 邰千慧 崔巍[1] 吴开春 惠晓丽[1] Luo Yingying;Liu Jingtao;Lei Zhijie;Zhang Haiping;Tai Qianhui;Cui Wei;Wu Kaichun;Hui Xiaoli(Department of Geriatric Endocrinology,The First Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710061,China;Afiliated No.986 Hospital of Xijing Hospital,Air Force Medical University,Shaanxi Xi’an 710054,China;Xjing Hospital of Digestive Diseases&State Key Laboratory of Cancer Biology,Air Force Medical University,Shaanxi Xi’an 710032,China)

机构地区：[1]西安交通大学第一附属医院老年内分泌科,陕西西安710061 [2]空军军医大学西京医院附属986医院核医学科,陕西西安710054 [3]空军军医大学西京消化病医院,肿瘤生物学国家重点实验室,陕西西安710032

出　　处：《现代肿瘤医学》2020年第1期3-8,共6页Journal of Modern Oncology

基　　金：国家自然科学基金创新研究群体项目(编号:81421003);国家自然科学基金项目(编号:30900704);陕西省重点研发计划一般项目(编号:2017SF-104,2018SF-161);陕西省科技攻关项目(编号:2013K12-09-03);陕西省卫生计生科研基金项目(编号:2016D066);西安市科技计划项目[编号:201805095YX3SF29(6)]

摘　　要：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,100~200μmol/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。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.

关 键 词：胃癌 抗血管生成 GX1二聚体 GX1单体 

分 类 号：R735.2[医药卫生—肿瘤]