罗勒多糖对肝癌细胞缺氧模型组蛋白去甲基化酶LSD1、JMJD2B及JARID1B表达的影响  

Effect of basil polysaccharide on the expression of histone demethylase LSD1,JMJD2B and JARID1B in hepatoma cells under hypoxic conditions

作　　者：冯兵[1,2,3] 朱莹 贺嵩敏 郑广娟 刘映[1] 朱亚珍 

机构地区：[1]广州中医药大学第二临床医学院,广东广州510006 [2]广东省中医医院,广东广州510120 [3]广东省中医药科学院,广东广州510006

出　　处：《时珍国医国药》2015年第8期1835-1840,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金项目(No.81202960;No.81403142);加拿大泰瑞.福克斯癌症科研基金资助(No.YN2014TF04)

摘　　要：目的研究罗勒多糖对肝癌细胞MHCC97H和MHCC97L缺氧模型组蛋白去甲基化酶LSD1、JMJD2B及JARID1B表达的影响,探讨罗勒多糖抗肿瘤侵袭转移作用与表观遗传修饰的关系。方法采用二氯化钴诱导肝癌细胞缺氧,建立肝癌细胞MHCC97H和MHCC97L体外缺氧模型,通过不同剂量罗勒多糖干预24h,细胞划痕实验检测缺氧条件下肝癌细胞的迁移能力,实时荧光定量PCR法检测各组肝癌细胞中HIF-1α、LSD1、JMJD2B及JARID1B mRNA表达水平,Westernblot法检测各组肝癌细胞中HIF-1α、LSD1、JMJD2B及JARID1B蛋白表达情况。结果罗勒多糖能抑制缺氧条件下MHCC97H和MHCC97L细胞的迁移能力,下调细胞中HIF-1αmRNA及蛋白的表达水平,与缺氧模型组相比有显著性差异(P<0.05);罗勒多糖能够下调MHCC97H细胞缺氧条件下LSD1、JMJD2B、JARID1B mRNA和蛋白的表达,与缺氧模型组相比有显著性差异(P<0.05);缺氧条件下MHCC97L细胞中LSD1、JMJD2B、JARID1B mRNA和蛋白的表达与正常对照组无显著性差别(P>0.05),罗勒多糖对这三种酶的表达亦无显著作用。结论罗勒多糖能改善不同转移潜能肝癌细胞MHCC97H和MHCC97L的缺氧微环境,抑制肿瘤细胞的侵袭转移。其中罗勒多糖对高转移潜能肝癌细胞MHCC97H的抗侵袭转移作用与其对细胞中组蛋白去甲基化酶LSD1、JMJD2B、JARID1B的调节有关,而对低转移潜能肝癌细胞MHCC97L侵袭转移能力的调节未发现与LSD1、JMJD2B、JARID1B有明显关系。Objective To study the effect of basil polysaccharide on the expression of histone demethylase LSD1,JMJD2B and JARID1B in hepatoma cells MHCC97 H and MHCC97 L under hypoxic conditions,to investigate the relationship between anti-metastasis of basil polysaccharide and epigenetic modifications. Methods Cobalt chloride（ CoCl2） simulating hypoxia was used,to establish MHCC97 H and MHCC97 L hepatoma cells hypoxia model in vitro,by different doses of basil polysaccharide intervened 24 hour. The migration ability of hepatoma cells under hypoxia condition was detected by cell wound scratch assay. The expression of HIF-1 alpha,LSD1,JMJD2B and JARID1B mRNA of hepatoma cells were detected by real time fluorescent quantitative PCR.The expression of HIF-1 alpha,LSD1,JMJD2B and JARID1B protein was detected by Western-blot method. ResultsBasil polysaccharide can inhibit the migration ability of MHCC97 H and MHCC97 L cells under hypoxia and can down-regulate of the expression of mRNA and protein of HIF-1 alpha in cells.Basil polysaccharide can down regulate the expression of mRNA and protein of LSD1,JMJD2B,JARID1B in MHCC97 H cells under hypoxia condition. The expression of mRNA and protein of LSD1,JMJD2B,JARID1B have no significant difference between hypoxia group and control group of MHCC97 L cells.Basil polysaccharide also has no significant effect on the expression of LSD1,JMJD2B,JARID1B in MHCC97 L cells. ConclusionBasil polysaccharide can improve the hypoxic microenvironment of MHCC97 H and MHCC97 L lines which have different metastatic potential,and can inhibit tumor cell invasion and metastasis. Through down-regulated the expression of LSD1,JMJD2B and JARID1B,basil polysaccharide can inhibit the invasion and metastasis of MHCC97 H cells.But in MHCC97 L cells,there is no obvious relationship between the cell invasion ability and the expression of LSD1,JMJD2B,JARID1B.

关 键 词：罗勒多糖 组蛋白去甲基化酶 赖氨酸特异性去甲基化酶1 JMJD2B JARID1B 

分 类 号：R962[医药卫生—药理学]