新生血管抑制与白介素12基因协同对原发性肝癌治疗研究

To he models of implanted rat liver cancer and diethylnitrosamina(DENA) induced rat liver cancer were treated with β-chclodextrin tetradecasufate (β-CD-14S) and retrovirus vector packaging cell that combined murine interleukin 12 and interleukin 2 fusion genes in this study. To exactly calculated the degree and the situation of microvessel endothelial cell (MEC) migration, 3H-TDR method in vitro and MEC migration mathematic formula were used after bio-determination of β-CD-14S. The results showed that β-CD-14S inhibited significantly the growth of endothelial cell and the formation of new vessel cell. In the experiment of implanted rat liver cancer, the survive rat was prolonged markedly and blood supply of artery and vein was decreased significantly. The retroviral vector encoding mIL-12 and hIL-2 was constructed, then transfected it into packaging cell line for screening the high titer virus and the high expression packaging cell strain (PA317+IL-12+IL-2). Treating the rat cancer with this packaging cell, the cancer could be cured or survive time would be prolonged in therapeutic groups. Even if the liver cancer was not cured, the survive time would be prolonged companying with improvement of immunity, after injection packaging cell into spleen that was safe method. The statistics was not significant in combine the both IL fusion gene and β-CD-14S, but the result was better than that of treatment with β-CD-14S alone..

本研究应用Ｂ环糊精１４硫酸脂携带ＴＮＰ４７０联合白介素１２融合基因的逆转录病毒包装细胞株对亚硝胺类药物诱发肝癌治疗，探索Ｂ－ＣＤ－１４Ｓ携带ＴＮＰ４７０影响血管内皮细胞增殖，抗新生血管形成和ＩＬ－１２来激活机体免疫，活化巨噬细胞作用。通过抑制新生血管形成药物肝动脉注射和ＩＬ－１２基因脾内注射门静脉途径的协同作用，寻找出联合用药治疗肝癌的新思路。