CXC趋化因子受体2受体拮抗剂SCH527123对胃癌细胞增殖迁移抑制作用及机制  

Inhibitory effect of CXC chemokine receptor 2 antagonist SCH527123 on proliferation and migration of gastric carcinoma cells

作　　者：蔡秀琴[1] 何俊飞 刘其龙[1] 黎文峰[1] 杨世斌[1] Cai Xiuqin;He Junfei;Liu Qilong;Li Wenfeng;Yang Shibin(Department of Gastrointestinal Surgery,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院胃肠外科,广州510080

出　　处：《中华实验外科杂志》2022年第6期1098-1101,共4页Chinese Journal of Experimental Surgery

摘　　要：目的探究CXC趋化因子受体2(CXCR2)的特征以及SCH527123对胃癌细胞增殖迁移的抑制作用及其机制。方法对中山大学附属第一医院156例临床标本进行免疫组织化学实验, 并培养胃癌细胞株HGC27, 检测其增殖、侵袭和血管生成变化。同时通过移植皮下肿瘤进一步研究SCH527123在胃癌中的作用。计量资料组间比较采用t检验。结果 CXCR2在胃癌中的表达上调(73.21%比35.71%, χ^(2)=21.656, P<0.01), 并且与预后不良相关(Log-rank 3.652, P<0.05)。体外实验结果显示, CXCR2拮抗剂SCH527123通过调节蛋白激酶B(Akt)、细胞外信号调节激酶(ERK)1/2和核因子-κB(NF-κB)通路抑制胃癌细胞的增殖、侵袭和血管形成(P<0.01)。体内实验结果显示, SCH527123抑制皮下移植瘤进展[(186.29±61.36) mm3比(351.13±195.75) mm3, t=3.936, P<0.01], 减少肿瘤微血管密度和肺转移的发生(15.33±5.51比65.00±7.94, t=8.904, P<0.01)。结论 CXCR2在胃癌的发展中起重要作用, 其拮抗剂SCH527123是一种有效的肿瘤抑制因子, 而Akt、ERK1/2和NF-κB通路可能是其作用机制。Objective To explore the characteristics of CXC chemokine receptor 2(CXCR2)and the inhibitory effect of SCH527123 on the proliferation and migration of gastric cancer cells.Methods A total of 156 clinical samples from our hospital was studied by immunohistochemistry.Gastric cancer cell line HGC27 was cultured to detect the variation of proliferation,invasion and angiogenesis.Subcutaneous tumors were transplanted to further study the role of SCH527123 in gastric carcinoma in vivo.T test was used for comparison between measurement data groups.Results Clinical data revealed that expression of CXCR2 was up-regulated in gastric cancer(73.21%vs.35.71%,χ^(2)=21.656,P<0.01)and was associated with poor prognosis(Log-rank 3.652,P<0.05).In vitro,CXCR2 antagonist SCH527123 inhibited proliferation,invasion and small tube formation of gastric cancer cells by regulating protein kinase B(Akt),extracellular signal-regulated kinase(ERK)1/2 and nuclear factor-κB(NF-κB)pathways(P<0.01).In vivo,SCH527123 inhibited subcutaneous tumor development[(186.29±61.36)mm3 vs.(351.13±195.75)mm3,t=3.936,P<0.01],decreased tumor microvessel density and lung metastasis(15.33±5.51 vs.65.00±7.94,t=8.904,P<0.01).Conclusion CXCR2 plays an important role in the development of gastric carcinoma and its antagonist SCH527123 is believed to act as an effective tumor suppressor.Akt,ERK1/2 and NF-κB pathways may be involved in the action mechanism.SCH527123 can be a potential drug with a bright future.

关 键 词：胃癌 CXC趋化因子受体2 

分 类 号：R735.2[医药卫生—肿瘤]