LAMP2抑制肝癌细胞增殖的机制  

The mechanism of proliferative inhibition of LAMP2 in liver cancer

作　　者：蔡维乐 王璐[1] 周霞[1] 卢萌萌[1] 候宇[1] 杨琼[1] 周新民[1] 

机构地区：[1]第四军医大学西京医院消化科,陕西西安710032

出　　处：《现代肿瘤医学》2017年第9期1365-1369,共5页Journal of Modern Oncology

摘　　要：目的:探索LAMP2分子对肝癌细胞增殖的影响及其机制。方法:首先利用Western blot及QT-PCR技术检测在不同肝癌细胞系中LAMP2分子的表达水平,然后选择一种肝癌细胞系HepG2进行慢病毒转染以建立LAMP2沉默的稳定细胞系HepG2-9455。利用MTT法对比LAMP2沉默细胞系和未沉默细胞系细胞的增殖情况。检测其可能影响的几个关键信号通路分子如PI3K、AKT、NF-κB、ERK等以明确其作用机制。结果:LAMP2在各肝癌细胞系中普遍表达较高,其在正常肝组织中主要分布于胆管周围并且呈极性分布,然而在肝癌组织中LAMP2的定位却发生了紊乱。通过慢病毒构建的稳定细胞系HepG2-9455其LAMP2表达下降了90%,而在下调LAMP2后可以显著抑制肝癌细胞HepG2的增殖。并且在下调LAMP2分子后HepG2细胞的PI3K、AKT和NF-κB分子发生明显下调。结论:LAMP2分子可以通过调节下游的PI3K、NF-κB(pp65)分子而影响肿瘤细胞的增殖。提示LAMP2分子在肝癌的恶性进展中可能发挥了重要的作用。Objective：To explore the effect of LAMP2 on the growth of liver cancer cells and the mechanism of it.Methods：Western blot was applied to measure the expression of LAMP2 in the different liver cancer cells.Then HepG2 cells were transfected with negative lentivirus or positive lentivirus which can downregulate mRNA of LAMP2,and we named the knock down cell lines as HepG2-9455.MTT method was used to contrast the differences of proliferation between the negative control cells and HepG2-9455 cells.Finally,to illuminate the mechanism of proliferative inhibition by downregulating LAMP2 in liver carcinoma cells,we examined some signal pathway proteins which were important in tumor progression,such as PI3K,NF-κB and ERK.Results：The expression of LAMP2 in HCC cells was high and the distribution also was disorganized in the hepatocarcinoma tissue.The proliferation of liver cancer cells could be significantly suppressed by downregulating LAMP2,and this phenomenon may be closely related to PI3K and NF-κB.Conclusion：LAMP2 could inhibit the growth of hepatoma cells by decreasing the activation of PI3K and NF-κB（p-p65）,which remind us that LAMP2 plays an important role and may be used as a potential therapeutic target for HCC.

关 键 词：LAMP2 肝癌 增殖 PI3K NF-ΚB 

分 类 号：R735.7[医药卫生—肿瘤]