摘要
目的:探讨山奈酚(kaempferol,KF)对胃癌细胞顺铂化疗敏感性及细胞迁移的影响及机制。方法:采用慢病毒转染构建稳定低表达肥胖相关蛋白(fat mass and obesity-associated protein,FTO)的人胃癌细胞AGS。将细胞分为对照组、山奈酚组、顺铂组、山奈酚+顺铂组、空载组、FTO低表达组、顺铂+空载组、顺铂+FTO低表达组、山奈酚+顺铂+空载组、山奈酚+顺铂+FTO低表达组。CCK-8法及平板克隆实验检测各不同处理对细胞增殖的影响;Transwell迁移实验检测不同处理对细胞迁移的影响。免疫印迹和实时荧光定量PCR检测FTO的表达。应用CB-Dock2在线工具分析山奈酚与FTO之间的分子对接情况。结果:山奈酚呈时间剂量依赖性抑制胃癌细胞的增殖能力,且显著增强胃癌细胞对顺铂的化疗敏感性,抑制胃癌细胞的迁移能力(P<0.05)。山奈酚可有效抑制胃癌细胞内FTO表达水平,低表达FTO则抑制细胞增殖和迁移能力(P<0.05)。与对照组相比,FTO的抑制消除了山奈酚对胃癌细胞顺铂化疗敏感性及迁移的影响(P<0.05)。此外,分子对接结果显示山奈酚与FTO之间有5个相互结合的活性口袋。结论:山奈酚通过抑制FTO的表达增强胃癌细胞顺铂化疗敏感性并抑制细胞迁移。
Objective:To investigate the effect and mechanism of kaempferol on cisplatin sensitivity and cell migration in gastric cancer cells.Methods:Human gastric cancer cells AGS with stable low expression of FTO were constructed by lentivirus transfection.The cells were divided into control group,kaempferol group,cisplatin group,kaempferol+cisplatin group,empty vector group,low expression group of FTO,cisplatin+empty vector group,low expression group of cisplatin+FTO,kaempferol+cisplatin+empty vector group,kaempferol+cisplatin+FTO low expression group.The effects of different treatments on cell proliferation were detected by CCK-8 assay and plate cloning assay.Transwell migration assay was used to determine the effect of different treatments on cell migration.Western blot and real-time fluorescent quantitative PCR were used to detect FTO expression.The CB-Dock2 online tool was applied to analyze the molecular docking between kaempferol and FTO.Results:Kaempferol inhibited the proliferation of gastric cancer cells in a time and dose dependent manner,and significantly enhanced the chemosensitivity of gastric cancer cells to cisplatin,and suppressed cell migration(P<0.05).Kaempferol could effectively inhibit the expression of FTO in gastric cancer cells,and the low expression of FTO inhibited cell proliferation and migration(P<0.05).Compared with the control group,inhibition of FTO eliminated the effects of kaempferol on cisplatin chemotherapy sensitivity and migration of gastric cancer cells(P<0.05).In addition,molecular docking results showed that there were five binding pockets between kaempferol and FTO.Conclusion:Kaempferol enhances the cisplatin chemotherapy sensitivity and inhibits the cell migration by suppressing FTO expression in gastric cancer cells.
作者
陈形梅
朱丽叶
黄珊珮
宁绮婷
韦二丹
覃丽霏
丘新泽
刘诗权
CHEN Xingmei;ZHU Liye;HUANG Shanpei;NING Qiting;WEI Erdan;QIN Lifei;QIU Xinze;LIU Shiquan(Department of Gastroenterology,the Second Affiliated Hospital of Guangxi Medical University,Guangxi Nanning 530007,China)
出处
《现代肿瘤医学》
2025年第5期724-732,共9页
Journal of Modern Oncology
基金
国家自然科学基金项目(编号:82260579)
广西中医药适宜技术开发与推广项目(编号:GZSY21-56)。
关键词
山奈酚
FTO
胃癌
化疗敏感性
迁移
Kaempferol
FTO
gastric cancer
chemotherapy sensitivity
migration
作者简介
陈形梅(1999-),女,壮族,广西贵港人,在读硕士研究生,主要从事消化道肿瘤的发病及转移机制研究。E-mail:1164257822@qq.com;通信作者:刘诗权(1975-),男,湖北大冶人,主任医师,主要从事消化道肿瘤的临床与基础研究。E-mail:poempower@163.com。
