E7010对原位移植鼠结肠38肿瘤的同基因C57BL/6小鼠肝转移及寿命的影响。

Effect of E7010 on liver metastasis and life span of syngeneic C57BL/6 mice bearing orthotopically transplanted murine Colon 38 tumor.

作者信息

Funahashi Y, Koyanagi N, Kitoh K

机构信息

Tsukuba Research Laboratories, Eisai Co. Ltd, Ibaraki, Japan.

出版信息

Cancer Chemother Pharmacol. 2001;47(2):179-84. doi: 10.1007/s002800000199.

DOI:10.1007/s002800000199

PMID:11269745

Abstract

PURPOSE

E7010 is an orally active sulfonamide antitumor agent showing good activity against various subcutaneously inoculated rodent tumors and human tumor xenografts. The purpose of this study was to evaluate the effect of E7010 on liver metastasis and life span of mice bearing orthotopically transplanted murine Colon 38 tumor.

METHODS

Orthotopic transplantation of murine Colon 38 tumor as intact tissue yielded hepatic metastasis with a high incidence in about 1 month in C57BL/6 mice, and the mice died in about 2 months with cachexia. In this model, the maximum tolerated dose of E7010 (100 mg/kg per day) was administered orally on various schedules, including for 14 days or daily until death, starting at 14 days after transplantation, or for 8 days from 21 days after transplantation.

RESULTS

E7010 showed tumor growth inhibition (T/C=40%) at the orthotopic site similar to that at the subcutaneous site (T/C = 32%) when administered from 14 days after transplantation. When E7010 was started from 21 days after transplantation, it significantly decreased the number of hepatic metastases (control 17.1+/-20.8, E7010 2.6+/-5.3), although inhibition of tumor growth at the orthotopic site was only moderate (T/ C=60%). The administration of E7010 until death produced a significant increase in life span (control 49.8+/-8.9 days, E7010 62.5+/-6.1 days). Although the tumor weight of the E7010-treated group on the day of death was similar to that of the untreated group (control 1.166+/-0.507 g, E7010 1.211+/-0.632 g), there were significantly fewer liver metastases in the E7010-treated group (control 41.3+/-31.1, E7010 2.0+/-2.0).

CONCLUSION

E7010 suppressed tumor growth at both primary and metastatic sites and increased life span in an orthotopic transplantation model of murine Colon 38 tumor in syngeneic C57BL/6 mice. Hepatic metastasis was inhibited more effectively than the growth of the primary tumor.

摘要

目的

E7010是一种口服活性磺胺类抗肿瘤药物，对各种皮下接种的啮齿动物肿瘤和人肿瘤异种移植瘤均显示出良好的活性。本研究的目的是评估E7010对原位移植鼠结肠38肿瘤小鼠肝转移和生存期的影响。

方法

将鼠结肠38肿瘤完整组织原位移植，在C57BL/6小鼠中约1个月内肝转移发生率较高，小鼠在约2个月内因恶病质死亡。在该模型中，从移植后14天开始，按不同给药方案口服给予E7010的最大耐受剂量（每天100mg/kg），包括给药14天或每日给药直至死亡，或从移植后21天开始给药8天。

结果

从移植后14天开始给药时，E7010在原位部位显示出与皮下部位相似的肿瘤生长抑制作用（T/C = 40%，皮下部位T/C = 32%）。当从移植后21天开始给予E7010时，它显著减少了肝转移灶的数量（对照组17.1±20.8，E7010组2.6±5.3），尽管原位部位的肿瘤生长抑制作用仅为中等程度（T/C = 60%）。给药E7010直至死亡显著延长了生存期（对照组49.8±8.9天，E7010组62.5±6.1天）。虽然E7010治疗组在死亡当天的肿瘤重量与未治疗组相似（对照组1.166±0.507g，E7010组1.211±0.632g），但E7010治疗组的肝转移灶明显较少（对照组41.3±31.1，E7010组2.0±2.0）。