Cao H, Tao P
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Zhonghua Yi Xue Za Zhi. 2001 Aug 25;81(16):1004-7.
To find out reliable index for evaluating the anti-hepatitis B virus (HBV) effects in vitro of lamivudine (3TC) and other five anti-HBV drugs.
The contents of human hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus DNA (HBV DNA) in the culture supernatant of 2.2.15 cell line transfected with hepatitis B virus gene were tested after the six anti-hepatitis B virus drugs were added respectively, and the accordance of different indexes was compared.
All six drugs, within a certain range, exercised only weak or no inhibitive effect on extracellular HBsAg and HBeAg secreted by 2.2.15 cell line. Lamivudine and 2 3-dideoxy-3-fluoroguanosine (FLG) significantly inhibited the level of HBV DNA, with the 50% inhibition concentration(IC50) of 0.31 mumol/L and 0.53 mumol/L respectively. Acyclovir (ACV) and interferon-alpha(IFN-alpha) also inhibited the HBV DNA with the IC50 of 0.33 mmol/L and 96.18 U/ml respectively. Phosphonoformate (PFA) and ribavirin (RBV) showed none effect on HBV DNA content even at the maximum non-toxic concentrations.
There is not accordance between the expression activities of proteins of HBsAg and HBeAg and the inhibition of HBV DNA level. HBV DNA level better reflexes the inhibitive effect of different drugs and can be used as an important index for evaluation of anti-HBV effect in vitro.
寻找评价拉米夫定(3TC)及其他五种抗乙肝病毒药物体外抗乙肝病毒(HBV)效果的可靠指标。
分别加入六种抗乙肝病毒药物后,检测转染乙肝病毒基因的2.2.15细胞系培养上清液中乙肝表面抗原(HBsAg)、乙肝e抗原(HBeAg)和乙肝病毒DNA(HBV DNA)的含量,并比较不同指标的一致性。
六种药物在一定范围内对2.2.15细胞系分泌的细胞外HBsAg和HBeAg仅有微弱抑制作用或无抑制作用。拉米夫定和2,3-二脱氧-3-氟鸟苷(FLG)显著抑制HBV DNA水平,50%抑制浓度(IC50)分别为0.31μmol/L和0.53μmol/L。阿昔洛韦(ACV)和干扰素-α(IFN-α)也抑制HBV DNA,IC50分别为0.33mmol/L和96.18U/ml。膦甲酸钠(PFA)和利巴韦林(RBV)即使在最大无毒浓度下对HBV DNA含量也无影响。
HBsAg和HBeAg蛋白的表达活性与HBV DNA水平的抑制之间不存在一致性。HBV DNA水平能更好地反映不同药物的抑制作用,可作为评价体外抗HBV效果的重要指标。