NOVEL APPROACHES WITH HEPATITIS B CORE CARRIER IN THE GROWTH CONTROL OF HepG2 BY BLOCKADE OF INSULIN-LIKE GROWTH FACTOR-Ⅰ RECEPTOR (IGF-IR)
In the middle of 1980s, hepatitis B virus core (HBc) gave onset to icosahedral virus-like particle (VLP) as a basic class of non-infectious carrier of foreign sequences. Insertion of foreign epitopes into the major immunodominant region (MIR) displays the epitopes on the surface of particle and guarantees a high level of specific B cell and T cell immunogenicity. In this study, we attempted to use the HBc particle as a good carrier for displaying the ligand blocking the insulin-like growth factor-I receptor-ligand interaction which played critical role in tumorogenesis and cancer cell proliferation. Genes coding for the ligand E5 (EPFRS PDLAL ETYG) to the insulin-like growth factor-Ⅰ/Ⅱ receptor (IGF-Ⅰ/ⅡR) were inserted into the MIR of HBc carrier by genetic engineering and were expressed in E. coli, termed E5 - Bc. we established one murine monoclonal antibody (mAb) specific to the inserted ligand, named as ami - E5 - HBc mAb, using hybridoma techniques. To determine whether this mAb could potentially be the antineoplastic agent for hepatoblastoma cell line HepG2, we examined the effect of mAb on the growth of the cells in vitro. Events of the IGF - IR signal transduction pathways were also examined. The mAb caused a marked inhibition of cell growth in a dose-dependent manner. The IGF-Ⅰ induced stimulation of cell growth and activation of IGF - IR was also attenuated by anti -E5 -HBc mAb. These changes were accompanied by a concomitant attenuation of activation of Akt and mitogen-activated protein kinases. In summary, our data showed that the mAb inhibited the growth of HepG2 cells by attenuating IGF - IR signaling processes. And our study also provided a rationale for future use of HBc as a good display carrier for inducing body generating specific antibodies against the foreign sequences with internal insertions.
Hepatitis B virus core (HBc) virus-like particle (VLP) IGF- IR ligand monoclonal antibody (mAb) HepG2
Jing Kong Zhengyu Diao Xiaozhao Deng Hui Zhong Wenjuan Yao Xuefang Hu
College of Biological Science and Technology, China Pharmaceutical University,Nanjing 210009, China College of Life Science, Nanjing Normal University, Nanjing 210097, China Huadong Research Institute for Medicine and Biotechnics, Nanjing 210002, China
国际会议
The 4th International Forum on Post-genome Technologies(4IFPT)(第四届国际后基因组生命科学技术学术论坛)
杭州
英文
517-520
2006-09-25（万方平台首次上网日期，不代表论文的发表时间）