小G蛋白ARL8B是潜在的抗原发性胃低分化黏液样腺癌的药物作用靶标  

A small GTPase ARL8B as a potential drug target for treatment of primary gastric myxoid adenocarcinoma with low differentiation

作　　者：赵京凤 成钟[2] 王楠 任吉霞 赵晓宏 蔡大勇 谢勇 ZHAO Jing-feng;CHENG Zhong;WANG Nan;REN Ji-xia;ZHAO Xiao-hong;CAI Da-yong;XIE Yong

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所中草药物质基础与资源利用教育部重点实验室,北京100193 [2]山西医科大学基础医学院,太原030001 [3]聊城大学生命科学学院,山东252059

出　　处：《中国医药生物技术》2018年第3期201-206,共6页Chinese Medicinal Biotechnology

基　　金：国家自然科学基金(81473114);教育部"新世纪优秀人才支持计划"

摘　　要：目的发现更多表达小G蛋白ARL8B而ARL8A无表达的肿瘤细胞系,以扩大ARL8B在抗肿瘤药物研究中的应用范围。方法利用实时荧光定量PCR法测定一些肿瘤细胞系中的ARL8B/ARL8A的相对表达量;以ARL8A和ARL8B都表达的细胞系作对照,对新发现的只表达ARL8B的肿瘤细胞系实施siRNA降低ARL8B表达量,用CCK8法检测ARL8B表达量被降低后的细胞活力变化;用Western blot考察ARL8B表达量降低诱导肿瘤细胞凋亡的原因。结果发现MGC-803细胞表达ARL8B而ARL8A无表达,胃癌细胞系BGC-823和MKN-45均表达ARL8A和ARL8B。ARL8B被敲低后MGC-803细胞出现了明显的凋亡,BGC-823和MKN-45细胞无明显的凋亡出现。细胞自噬水平显著提高是引起细胞凋亡的原因。结论 MGC-803细胞系来源于胃低分化黏液样腺癌患者,是新发现的表达ARL8B而ARL8A无表达的肿瘤细胞系,降低ARL8B表达能导致明显的细胞凋亡,提示ARL8B是抗胃低分化黏液样腺癌潜在的药物作用靶标。Objective To identify more tumor cell lines expressing the small GTPase ARL8B but not ARL8A, and to understand more about the application of ARL8B in antitumor drug research. Methods Real-time fluorescence quantitative PCR was used to determine the relative expression levels of ARL8B/ARL8A in some tumor cell lines. The tumor cell line expressing ARL8B only were treated with siRNA to reduce ARL8B expression, then CCK8 was used to detect cell viability. The cell lines expressing both ARL8A and ARL8B were used as control. Western blot was used to examine the mechanism for the apoptosis induced by decreased ARL8B. Results Gastric cancer cell line MGC-803 was found to solely express ARL8B, while gastric cancer cell lines BGC-823 and MKN-45 expressed both ARL8A and ARL8B. After ARL8B knockdown, more obvious apoptosis was found in MGC-803 cells, than that in BGC-823 and MKN-45 cells. Significant increase of autophagy might be the cause of apoptosis. Conclusion The MGC-803 cell line, isolated from primary gastric myxoid adenocarcinoma with low differentiation, is identified to express only ARL8B. Decreasing the expression of ARL8B can lead to significant cell apoptosis, suggesting that ARL8B might be a potential drug target for the treatment of the primary gastric myxoid adenocarcinoma.

关 键 词：单体GTP结合蛋白质类 ADP核糖基化因子样蛋白8B 分子靶向治疗 自噬 原发性胃低分化黏液样腺癌 

分 类 号：R96[医药卫生—药理学]