Uadia P, Blair A H, Ghose T
Cancer Immunol Immunother. 1983;16(2):127-9. doi: 10.1007/BF00199245.
To study the mechanism of tumor inhibition, the uptake of methotrexate (MTX) covalently linked to a rabbit IgG antibody against a tumor-associated antigen on the surface of mouse EL4 lymphoma cells (AELG) has been compared with the uptake of free MTX and of MTX covalently linked to normal rabbit IgG (NRG). When EL4 cells were incubated at 37 degrees C with 10 microM free MTX uptake leveled off after 30 min, at 30 pmol/mg protein. In contrast, uptake of both conjugates under these conditions continued throughout an observation period of 6 h. At 6 h the net uptake of MTX bound to AELG was 40 pmol/mg protein and that of MTX bound to NRG was 24 pmol/mg protein. These results show that both MTX-AELG and MTX-NRG conjugates are taken up by EL4 cells. The rate at which EL4 cells took up bound MTX was much slower than that of free MTX but, at 6 h, the net uptake of MTX-AELG exceeded that of the free drug.
为研究肿瘤抑制机制,将与抗小鼠EL4淋巴瘤细胞(AELG)表面肿瘤相关抗原的兔IgG抗体共价连接的甲氨蝶呤(MTX)的摄取,与游离MTX以及与正常兔IgG(NRG)共价连接的MTX的摄取进行了比较。当EL4细胞在37℃下与10μM游离MTX孵育时,30分钟后摄取量趋于平稳,为30 pmol/mg蛋白质。相比之下,在这些条件下两种偶联物的摄取在6小时的观察期内持续进行。6小时时,与AELG结合的MTX的净摄取量为40 pmol/mg蛋白质,与NRG结合的MTX的净摄取量为24 pmol/mg蛋白质。这些结果表明,MTX-AELG和MTX-NRG偶联物均被EL4细胞摄取。EL4细胞摄取结合型MTX的速率比游离MTX慢得多,但在6小时时,MTX-AELG的净摄取量超过了游离药物。