Doong S L, Lin M H, Tsai M M, Li T R, Chuang S E, Cheng A L
Graduate Institute of Microbiology and Cancer Research Center, National Taiwan University, College of Medicine, Taipei, ROC.
J Hepatol. 1998 Dec;29(6):872-8. doi: 10.1016/s0168-8278(98)80113-x.
BACKGROUND/AIMS: Persistent hepatitis B virus (HBV) infection may cause hepatocellular carcinoma. Patients with hepatocellular carcinoma are characterized by nonresponsiveness to chemotherapeutic agents. While many studies have been devoted to understanding the hepatocarcinogenesis mechanism of HBV, the possible relationship between HBV and the drug sensitivity phenotype of cancer cells has rarely been addressed. The hepatitis B virus X gene encodes a transcription transactivator which has been suggested to be a potential factor in viral hepatocarcinogenesis. The role of HBV pX in mediating the drug resistance phenotype of hepatoma cell lines was examined in this study.
Standard transfection and chloramphenicol acetyltransferase assay were utilized to examine the effect of HBV pX transactivator on a reporter gene under the control of the human multidrug resistance (MDR) 1 upstream regulatory elements. Selected Hep G2 clones with or without HBV pX expression were tested for their sensitivity towards various anti-cancer agents by utilization of MTT assay.
The expression of HBV pX in both Hep G2 (p53+) and Hep 3B (p53-) cells resulted in transactivation of the reporter gene under control of the human MDR1 upstream regulatory elements. Northern blot analysis indicated that expression of the endogenous MDR1 gene was also elevated in Hep G2 clones with HBV pX expression. Decreased drug sensitivity towards adriamycin, vinblastine, and VP-16 was observed in Hep G2 clones with HBV pX expression.
HBV pX can transactivate the MDR1 gene. Drug sensitivity was altered in Hep G2 cells with HBV pX expression.
背景/目的：持续性乙型肝炎病毒（HBV）感染可能导致肝细胞癌。肝细胞癌患者的特征是对化疗药物无反应。虽然许多研究致力于了解HBV的肝癌发生机制，但HBV与癌细胞药物敏感性表型之间的可能关系很少被提及。乙型肝炎病毒X基因编码一种转录反式激活因子，该因子被认为是病毒肝癌发生的一个潜在因素。本研究检测了HBV pX在介导肝癌细胞系耐药表型中的作用。
利用标准转染和氯霉素乙酰转移酶测定法，检测HBV pX反式激活因子对人多药耐药（MDR）1上游调控元件控制下的报告基因的影响。通过MTT测定法，对选择的有或无HBV pX表达的Hep G2克隆进行各种抗癌药物敏感性测试。
HBV pX在Hep G2（p53 +）和Hep 3B（p53 -）细胞中的表达均导致人MDR1上游调控元件控制下的报告基因的反式激活。Northern印迹分析表明，在有HBV pX表达的Hep G2克隆中，内源性MDR1基因的表达也升高。在有HBV pX表达的Hep G2克隆中，观察到对阿霉素、长春碱和VP - 16的药物敏感性降低。
HBV pX可反式激活MDR1基因。有HBV pX表达的Hep G2细胞的药物敏感性发生改变。
