乙型肝炎病毒X蛋白上调环加氧酶2表达促进肝癌细胞增殖的实验研究  

X Protein of the Hepatitis B Virus Promotes the Proliferation of Hepatoma Cells by Upregulating Cyclooxygenase-2 Expression:An Experimental Study

作　　者：元顺女 朴美花 金丹[2] YUAN Shunnyu;PIAO Meihua;JIN Dan(The Affiliated Hospital of Yanbian University,Yanbian 133002,China;Yanji City Hospital,Yanji 133000,China)

机构地区：[1]延边大学附属医院,延边133002 [2]延吉市医院,延吉133000

出　　处：《病毒学报》2022年第3期620-626,共7页Chinese Journal of Virology

摘　　要：乙肝病毒X蛋白(Hepatitis B virus X protein,HBx)高表达与乙肝相关肝癌的发病密切相关,但HBx发挥促癌作用的机制并不清楚。环加氧酶2(Cyclooxygenase,COX2)具有促进肝癌细胞增殖的功能,乙肝相关肝癌中COX2的表达增加且与HBx呈正相关,提示上调COX2可能是HBx促进肝癌细胞增殖的分子机制。为了阐明HBx是否通过上调COX2促进肝癌细胞增殖,本实验培养了肝癌HepG2细胞并分为对照组、转染pcDNA3.1-HBx质粒的HBx组、转染NC siRNA的si-NC组、转染NC siRNA及pcDNA3.1-HBx质粒的si-NC+HBx组、转染COX2 siRNA及pcDNA3.1-HBx质粒的si-COX2+HBx组。检测细胞增殖活力OD_(490nm)的水平,COX2、B淋巴细胞瘤2基因(BCL2)、生存素(Survivin)的表达量,前列腺素E2(英文名,PGE2)的含量。实验结果显示,HBx组的OD_(490nm)水平,细胞中COX2、BCL2、Survivin的表达量,培养基中PGE2的含量均高于对照组;si-COX2+HBx组的OD_(490nm)水平,细胞中COX2、BCL2、Survivin的表达量,培养基中PGE2的含量均低于si-NC+HBx组。以上结果表明,HBx促进肝癌细胞增殖的作用部分由上调COX2表达所介导。本实验阐明了上调COX2在HBx促进肝癌细胞增殖中的作用,这为今后研究HBx发挥促癌作用的分子机制以及乙肝相关肝癌的发病机制提供了新思路。High expression of the X protein of the hepatitis B virus(Hepatitis B virus X protein,HBx)is closely related to the pathogenesis of hepatitis B virus(HBV)-related liver cancer.However,how HBx promotes cancer is not clear.Cyclooxygenase(Cyclooxygenase,COX)2 promotes the proliferation of hepatoma cells.COX2 expression in HBV-related liver cancer is increased and positively correlated with HBx,which suggests that the number of hepatoma cells is increased.We wished to ascertain if HBx promotes the proliferation of hepatoma cells by upregulating COX2 expression.HepG2 cells were cultured and five groups were created:control;HBx(cells transfected with pcDNA3.1-HBx plasmid);si-NC(cells transfected with NC siRNA);siNC+HBx(cells transfected with NC siRNA and pcDNA3.1-HBx plasmid);si-COX2+HBx(cells transfected with COX2 siRNA and pcDNA3.1-HBx plasmid).The proliferation,viability,optical density at 490 nm(OD_(490nm)),level of prostaglandin(PG)E2,as well as expression of COX2,B-cell lymphoma-2(B-cell lymphoma-2,BCL2)gene,and survivin were measured.OD_(490nm),expression of COX2,BCL2 and survivin in cells,and the PGE2 level in the culture medium of the HBx group were higher than those in the control group.OD_(490nm),expression of COX2,BCL2 and survivin in cells,and the PGE2 level in the culture medium of the siCOX2+HBx group were significantly lower than those of the si-NC+HBx group.These results suggested that the effect of HBx in promoting the proliferation of hepatoma cells was mediated(at least in part)by upregulation of COX2 expression.We elucidated the role of upregulation of COX2 expression in the way that HBx promotes the proliferation of hepatoma cells.Our data provide a new way to study the molecular mechanism of the role of HBx in promoting cancer,and the pathogenesis of HBV-related liver cancer.

关 键 词：乙肝相关肝癌 乙肝病毒X蛋白(HBx) 环氧合酶2(COX2) 前列腺素E2(PGE2) 细胞增殖 

分 类 号：R373.21[医药卫生—病原生物学]