Antimetastatic Effect of a Novel Indolocarbazole (NB-506) on IMC-HM Murine Tumor Cells Metastasized to the Liver

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Abstract
IMC‐HM cells were isolated from spontaneously induced ascitic IMC carcinoma cells that had been maintained intraperitoneally in CDF1 mice. Metastasis to the liver of subcutaneously implanted IMC‐HM cells was detected 10 days after implantation into the flanks of mice (day 10), but metastasis to other organs was limited. Thereafter, however, tumor cells spread rapidly to lymph nodes, lung, spleen, ovary and other organs, and the mice died on day 13 to 18. We report here, together with the properties of IMC‐HM cells, the effects of adriamycin, cisplatin, etoposide and a new indolocarbazole antitumor compound (NB‐506) on this model of metastasis. Although these anticancer agents all inhibited the growth of the subcutaneous tumors, their effects on the life span of the tumor‐bearing mice varied. Treatment with NB‐506, started on day 1, more than doubled the survival period at doses 30 mg/m2 to 900 mg/m2. Further, treatment with NB‐506, started on day 4 after resection of the primary tumor, inhibited growth of the metastasized tumor in the liver and other organs. Etoposide also increased the life span at a limited range of doses. However, the life‐prolonging effects of adriamycin and cisplatin were marginal. These results demonstrate that IMC‐HM carcinoma is a good model for spontaneous metastasis to the liver followed by lethal spread to many organs. Moreover, NB‐506 was found to be highly effective against the growth not only of subcutaneous tumors, but also of tumors metastasized to the liver.

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