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作 者:孟金凤 闫攀登 董志忠 MENG Jin-feng;YAN Pan-deng;DONG Zhi-zhong(Nutrition&Health Research Institute,COFCO Corporation,Beijing 102209,China;Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005,China;The State Key Lab of Proteomics,National Center for Protein Sciences,Institute of Radiation Medicine,Academy of Military Medical Sciences,Beijing 100850,China;Beijing Key Laboratory of Nutrition&Health and Food Safety,Beijing 102209,China)
机构地区:[1]中粮营养健康研究院有限公司,北京102209 [2]中国医学科学院北京协和医学院基础学院研究生院,100005 [3]军事科学院军事医学研究院辐射医学研究所蛋白质组学国家重点实验室,北京100850 [4]营养健康与食品安全北京市重点实验室,102209
出 处:《中国医药生物技术》2022年第6期503-511,共9页Chinese Medicinal Biotechnology
基 金:中国博士后科学基金面上项目(2016M601239)。
摘 要:目的为抑制肝癌转移或抗药性提供新的科学技术方法。方法采用siRNA技术在HCCLM3细胞系中敲低CAP2的表达,观测其对肝癌细胞系迁移、侵袭和耐药性的影响,并采用仿生模拟上消化道技术进一步评估siCAP2核酸分子经上消化道系统的稳定性。结果CAP2在肝癌组织中以及肝癌细胞系显著高表达。si CAP2显著抑制HCCLM3细胞的迁移和侵袭,si CAP2可促进HCCLM3凋亡,增强其对索拉菲尼、顺铂的药物敏感性。si CAP2在仿生模拟上消化道系统小肠消化2 h后的稳定性为29.8%~35.8%。对照组和抑制CAP2组在体外胃肠消化阶段其核酸含量显著下降,且siRNA和蛋白质或者脂肪溶液复配比单独和水混合在消化系统中的保留率更高。对照组和抑制CAP2组别之间无显著差异。结论siCAP2在HCCLM3发挥抑癌作用,并可以在仿生模拟消化系统中部分稳定保留。Objective To provide new scientific and technological methods for inhibiting liver cancer metastasis or drug resistance.Methods siRNA technology was used to knock down the expression of CAP2 in HCCLM3 cell lines and its effects on migration,invasion and drug resistance were observed. The stability of siCAP2 nucleic acid molecules through the upper gastrointestinal system was further evaluated by bionic upper gastrointestinal technology.Results CAP2 was highly expressed in liver cancer tissues and liver cancer cell lines. siCAP2 significantly inhibited the migration and invasion of HCCLM3 cells, promoted the apoptosis and enhanced its drug sensitivity to sorafenib and cisplatin. The stability of siCAP2 after 2 h of digestion in the small intestine of the biomimetic upper gastrointestinal system was about 29.8%-35.8%. The nucleic acid content of the control group and the inhibition CAP2 group decreased significantly during in vitro gastrointestinal digestion, and the retention rate of siRNA combined with protein or fat solution was higher than that of siRNA combined with water alone. There was no significant difference between the control group and the CAP2 inhibition group.Conclusion siCAP2 acts as a tumor suppressor in HCCLM3 cells and can be partially stably retained in the biomimetic digestive system.
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