Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model
Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model
复制标题
DOI：
10.1111/j.1442-2042.2004.00855.x
复制
发表时间：
2004-08-01
影响因子：
2.6
通讯作者：
Kamidono, S
中科院分区：
文献类型：
--
作者：
Hikosaka, S;Hara, I;Kamidono, S
背景资料：本研究的目的是评估白细胞介素12（IL-12）和IL-18基因同时导入小鼠膀胱癌细胞系（MBT 2）的抗肿瘤作用。我们的目的是比较这些与任何一个基因单独和调查的机制，通过转移IL-12和/或IL-18基因在这个模型system.Methods：我们转染IL-12和/或IL-18基因到MBT 2细胞通过脂质体介导的基因转移方法。我们通过酶联免疫吸附试验证实了IL-12和/或IL-18的分泌。将亲本（MBT 2/P）、IL-12转染的（MBT 2/IL-12）、IL-18转染的（MBT 2/IL-18）或IL-12和IL-18两者转染的（MBT 2/两者）细胞皮下或静脉内注射到同系C3 H小鼠中。结果：MBT 2/IL-12、MBT 2/IL-18和MBT 2/Both经皮下或静脉注射给同系小鼠后，均被完全排斥。而MBT 2/IL-18不能在裸鼠体内生长。此外，MBT 2/IL-18的抗肿瘤作用在注射到NK细胞通过抗体处理耗尽的裸鼠中时被部分消除。结论：NK细胞和T细胞分别通过分泌IL-12和IL-18发挥抗肿瘤作用，MBT 2/Both同时具有两种机制。
Background: The objectives of this study were to evaluate the antitumor effects of the simultaneous introduction of interleukin 12 (IL-12) and IL-18 genes into a mouse bladder cancer cell line (MBT2). We intended to compare these with those of either gene alone and to investigate the mechanism of the effects induced by the transfer of IL-12 and/or IL-18 genes in this model system.Methods: We transfected the IL-12 and/or IL-18 genes into MBT2 cells by the liposome-mediated gene transfer method. We confirmed the secretion of IL-12 and/or IL-18 by enzyme-linked immunosorbent assay. Parental (MBT2/P), IL-12-transfected (MBT2/IL-12), IL-18-transfected (MBT2/IL-18) or both IL-12- and IL-18-transfected (MBT2/Both) cells were subcutaneously or intravenously injected into syngeneic C3H mice. To analyze the mechanism of tumor rejection, these clones were subcutaneously injected into naive nude mice and those depleted with natural killer (NK) cells by antibody.Results: MBT2/IL-12, MBT2/IL-18 and MBT2/Both were completely rejected when they were injected subcutaneously or intravenously into syngeneic mice. However, MBT2/IL-12, but not MBT2/IL-18, could grow in nude mice. Moreover, the antitumor effect of MBT2/IL-18 was partially abrogated when injected into nude mice of which NK cells were depleted by antibody treatment. MBT2/Both was completely rejected in both nude mice with and without NK cells.Conclusion: The results of the present study indicate that T cells and NK cells seem to play important roles in the antitumor effects by the secretion of IL-12 and IL-18, respectively, and MBT2/Both possesses both mechanisms.