Shinohara T, Sugimoto Y, Sato S, Sone S, Tsuruo T
Cancer Chemotherapy Center, Japanes Foundation for Cancer Research, Tokyo.
Jpn J Cancer Res. 1997 Nov;88(11):1100-7. doi: 10.1111/j.1349-7006.1997.tb00335.x.
In the present study, we examined the effect of interleukin-2 (IL-2) gene transfer into multidrug resistance (MDR) cancer cells on the therapeutic efficacy of MRK16. Human MDR ovarian cancer cells, AD10, were transduced with a bicistronic IL-2 retrovirus, Ha-IL2-IRES-Neo. The G418-resistant population, IL2-AD10, secreted IL-2 into the culture supernatant and did not form a tumor mass in nude mice. The IL2-AD10 cells were more susceptible to the cytotoxicity of murine spleen cells than AD10 cells in vitro. For examination of the effect of IL-2 gene transfer on the antitumor activity of MRK16 against P-glycoprotein-positive tumors, IL2-AD10 cells were co-transplanted s.c. with AD10 cells into nude mice in a ratio of 1:3, and the mice were treated with MRK16 on days 2 and 7. MRK16 markedly inhibited the growth of AD10 cells mixed with IL2-AD10 cells under conditions (0.3-1 microgram/body) where it showed only marginal effects on the growth of AD10 tumors. These findings suggest that IL-2 gene transfer potentiates the antitumor activity of MRK16 against MDR tumors.
在本研究中，我们检测了将白细胞介素-2（IL-2）基因导入多药耐药（MDR）癌细胞对MRK16治疗效果的影响。用双顺反子IL-2逆转录病毒Ha-IL2-IRES-Neo转导人MDR卵巢癌细胞AD10。对G418耐药的细胞群体IL2-AD10将IL-2分泌到培养上清中，并且在裸鼠中不形成肿瘤块。在体外，IL2-AD10细胞比AD10细胞对鼠脾细胞的细胞毒性更敏感。为了检测IL-2基因转移对MRK16抗P-糖蛋白阳性肿瘤的抗肿瘤活性的影响，将IL2-AD10细胞与AD10细胞按1:3的比例皮下共移植到裸鼠中，并在第2天和第7天用MRK16治疗小鼠。在对AD10肿瘤生长仅显示边缘效应的条件（0.3-1微克/只）下，MRK16显著抑制了与IL2-AD10细胞混合的AD10细胞的生长。这些发现表明，IL-2基因转移增强了MRK16对MDR肿瘤的抗肿瘤活性。
