Inhibition of liver metastases and tumor cell invasion in spontaneous liver metastasis model (LMFS) by sodium D-glucaro-delta-lactam (ND2001)

We examined the inhibitory effect of sodium D-glucaro-delta-lactam (sodium 5-amino-5-deoxy-D-glucosaccharic acid-delta-lactam: ND2001) upon liver meta stases of the LMFS tumor. A permanent cell line, LMFS, was established from a spontaneously occurring murine retroperitoneal tumor of BALB/c mouse ori gin, and after a subcutaneous injection, the LMFS cells proliferated at the inoculation site (100% take) with liver metastases. ND2001 had little effe ct on the cell growth, cell cycle and phagokinesis of the LMFS cells in vit ro. However, when the invasive activity was measured by the Boydem chamber method, the number of LR IFS cells was reduced, with inhibition rates of 98 .0%. After the LMFS cells treated with ND2001 in vitro, the numbers of hepa tic metastases of subcutaneous inoculation of treated cells were reduced do se-dependently, and those of intravenous inoculation were not found by micr oscopical study. When the LMFS tumor-bearing mice were treated with ND2001 (0, 30, 100 mg/kg/d) from day 1, ND2001 (30 mg/kg) inhibited the liver meta stases with a rate of 56.4%, and when given from day 15, ND2001 (100 mg/kg) inhibited with a rate of 47.5%. But ND2001 showed neither cytocidal nor an titumor activity. Combination therapy of primary tumor resection and ND2001 administration revealed that preoperative use of ND2001 was more effective in preventing liver metastases. These results suggested that ND2001 might have a potential use as an anti-metastatic agent for operative patients wit hout metastasis. (C) 2000 Editions scientifiques et medicales Elsevier SAS.