Kashida T, Narasaki N, Sakai A, Tsujihara K, Tsuzurahara K, Naito K, Takeyama S
Research Laboratories, Tanabe Seiyaku Co. Ltd., Saitama, Japan.
Immunopharmacology. 1997 Aug;37(1):95-104. doi: 10.1016/s0162-3109(97)00039-8.
We investigated possible mechanisms of the antitumor action of gamma-(9H-purine-6-yl) thiomethyl L-glutamate (6-MPG), a water-soluble derivative of 6-MP. In the double grafted tumor system, BALB/c mice were inoculated intradermally with 10(6) cells of MethA fibrosarcoma at the right inguinal region on day 0 (the primary tumor) and later with 3 x 10(6) cells at the left on day 10 (the secondary tumor). Intraperitoneal administration of 6-MPG at a dose of 100 mg/kg/day from day 3 through 7 completely prevented growth of the secondary tumor. 6-MPG showed no effect on growth of colon 26 adenocarcinoma cells inoculated in place of the secondary MethA cells (antigen specificity). 6-MPG did not inhibit the secondary MethA growth in the BALB/c (nu/nu) mouse. The inhibitory effect of 6-MPG on the secondary tumor growth was diminished by prior treatment of the primed animals with cyclosporin A and anti-Thy antibody. Spleen cells from the tumor-bearing mice treated with 6-MPG showed a tumor-neutralizing activity (Winn assay). Treatment of the spleen cells with anti-CD8 antibody plus complement diminished the tumor-neutralizing effect but that with anti-CD4 antibody plus complement did not, indicating that CD8-positive cells are responsible for potentiation of the tumor immunity. These results suggest that the antitumor effect of 6-MPG against the secondary tumor is elicited by augmenting tumor specific T-cell production.
我们研究了6-巯基嘌呤（6-MP）的水溶性衍生物γ-（9H-嘌呤-6-基）硫甲基L-谷氨酸（6-MPG）抗肿瘤作用的可能机制。在双移植肿瘤系统中，于第0天在BALB/c小鼠右腹股沟区皮内接种10⁶个MethA纤维肉瘤细胞（原发肿瘤），并于第10天在左侧接种3×10⁶个细胞（继发肿瘤）。从第3天至第7天，以100mg/kg/天的剂量腹腔注射6-MPG可完全抑制继发肿瘤的生长。6-MPG对替代继发MethA细胞接种的结肠26腺癌细胞的生长无影响（抗原特异性）。6-MPG对BALB/c（nu/nu）小鼠的继发MethA生长无抑制作用。用环孢素A和抗Thy抗体预先处理致敏动物可减弱6-MPG对继发肿瘤生长的抑制作用。用6-MPG处理的荷瘤小鼠的脾细胞表现出肿瘤中和活性（Winn试验）。用抗CD8抗体加补体处理脾细胞可减弱肿瘤中和作用，而用抗CD4抗体加补体处理则无此作用，表明CD8阳性细胞负责增强肿瘤免疫。这些结果表明，6-MPG对继发肿瘤的抗肿瘤作用是通过增加肿瘤特异性T细胞的产生而引发的。
