肝癌免疫导向药物的内化  

Internalization of immunotargeting drugs against hepatoma

作　　者：隋延仿[1] 孙志伟[1] 陈志南[1] 刘彦仿[1] 王文亮[1] 

机构地区：[1]第四军医大学病理学教研室

出　　处：《第四军医大学学报》1997年第4期301-303,共3页Journal of the Fourth Military Medical University

基　　金：国家自然科学基金

摘　　要：目的：研究肝癌免疫导向药物的内化．方法：应用胶体金标记技术，对肝癌免疫导向药物ＨＡｂ１８－ＡＤＭ，ＨＡｂ２５－ＡＤＭ在靶细胞人肝癌细胞系ＳＭＭＣ－７７２１中的内化过程分别进行了电镜示踪研究．结果：８０％的靶细胞膜表面有金标记物结合；有金标记物结合的靶细胞内均见金标记物的内化，无金标记物结合的靶细胞内未见金标记物的内化．内化的途径均以非被覆小凹途径为主．金标记物内化入胞后，首先均定位于初始内吞泡中，并向胞内转运，同时发生泡－泡融合现象，形成较大的多泡小体，即胞内体．在Ｇｏｌｇｉ区，胞内体与Ｇｏｌｇｉ小泡融合，最后定位于次级溶酶体．当免疫导向药物与靶细胞３７℃孵育至１８ｈ，可见靶细胞胞浆空泡化，甚至坏死改变，而对照组细胞生长良好．结论：免疫导向药物进入靶细胞后，在溶酶体内发生降解，而后ＡＤＭ到达作用位点一细胞核内发挥细胞毒作用，ＨＡｂ１８－ＡＤＭ，ＨＡｂ２５－ＡＤＭ的内化为有效内化，具有良好的临床应用前景．Objective: To study the internalization of immunotargeting drug for hepatocellular carcinoma. Methods: By use of colloidal gold technique, the process of internalization of the immunotargeting drugs, HAb18 and HAb25, against hepatoma in the targeting cells of human hepatoma cell line SMMC 7721 was observed respectively under an electron microscope. Results: 80% of the target cells were conjugated with gold labeled particles on the cellular surfaces. The internalization of gold labeled particles were present in all of the target cells conjugated with gold labeled particles, while no any internalization of gold labeled particles could be seen in the target cells without conjugation of gold labeled particles. The main way of internalization was invariably through a non coated microinvagination. After entering into the cells, all of the gold labeled particles were first localized in the primary endocytic vacuoles, and then transferred intracellularly. Simultaneously, the appearance of vacuole vacuole fusion was present forming the larger multi vesicular bodies, the endosome. In the Golgi region, the endosome fused with the Golgic vacuoles, and finally localized in the secondary lysosomes. 18 h after the intercellular internalization of immunotargeting drugs, the cytoplasmic vacuolization could be visible, even cellular necrosis. The control cells grew well. Conclusion: After entering into the targeting cells, the immunotargeting drugs degrade within the lysosomes, then, ADM arrives at its function site and plays the role of cell toxicity intranuclearly. The internalization of HAb18 ADM and HAb25 ADM is effective, possessing a good prospect in clinical application.

关 键 词：肝肿瘤 内化 免疫导向药物 

分 类 号：R735.705[医药卫生—肿瘤]