Nishihara T, Tanaka S, Murakami M, Hirakawa M, Nagashima T
Dept. of Neurosurgery, Ichihara Hospital, Teikyo University School of Medicine.
Gan To Kagaku Ryoho. 1995 Aug;22(9):1197-202.
Recently, it has been reported that CDDP modifies the immune responses of tumor bearing hosts, but problem of the most appropriate treatment with CDDP to augment the host immunity remains unresolved. The purpose of this study was to determine the most advantageous administration of CDDP to increase both its cytotoxic effect and antitumor immune reactivity. Cell growth inhibition in vitro was assessed by MTT assay after treatment of U-251MG cells with various concentrations of CDDP for 24 or 120 hours. The results of this experiment showed that the growth of U-251MG cells in vitro was suppressed by CDDP in a dose-dependent as well as a time-dependent manner. Ten days after subcutaneous inoculation of human glioma cells, GL-9, in the rear flank of nude mice, they were assessed for growth suppression by CDDP. Totally, 20 ml/kg of CDDP was administered to each mouse; in one group (high-dose CDDP group), 5 ml/kg of CDDP on every fifth day, and in the other group (low-dose CDDP group), 2 ml/kg on every day. Measurement of the tumor volume in each group revealed no significant difference between the two groups in terms of the efficacy of tumor growth suppression. Twenty-one days after inoculation, we measured the splenic natural killer(NK) cell activity in each mouse. The results showed that NK cell activity was significantly increased in the low-dose cisplatin (2 ml/kg) group, and significantly decreased in the high-dose cisplatin (10 mg/ml) group, as compared to the control group. The results of our study suggest that the separate administration of low-dose CDDP is a useful treatment strategy for malignant glioma, because it increases the antitumor immune reactivity of hosts without decreasing the direct tumor cytotoxicity of CDDP.
最近，有报道称顺铂可改变荷瘤宿主的免疫反应，但关于顺铂增强宿主免疫力的最合适治疗问题仍未解决。本研究的目的是确定顺铂最有利的给药方式，以增强其细胞毒性作用和抗肿瘤免疫反应性。在用不同浓度的顺铂处理U-251MG细胞24或120小时后，通过MTT法评估体外细胞生长抑制情况。该实验结果表明，顺铂在体外对U-251MG细胞生长的抑制呈剂量依赖性和时间依赖性。将人胶质瘤细胞GL-9皮下接种于裸鼠后肢侧腹10天后，评估顺铂对其生长的抑制作用。每只小鼠总共给予20 ml/kg的顺铂；一组（高剂量顺铂组）每5天给予5 ml/kg的顺铂，另一组（低剂量顺铂组）每天给予2 ml/kg。测量每组的肿瘤体积发现，两组在肿瘤生长抑制效果方面无显著差异。接种21天后，我们测量了每只小鼠脾脏自然杀伤（NK）细胞活性。结果显示，与对照组相比，低剂量顺铂（2 ml/kg）组NK细胞活性显著增加，高剂量顺铂（10 mg/ml）组NK细胞活性显著降低。我们的研究结果表明，低剂量顺铂单独给药是恶性胶质瘤的一种有效治疗策略，因为它可增强宿主的抗肿瘤免疫反应性，而不降低顺铂对肿瘤的直接细胞毒性。
