Differential chemosensitivity of local and metastatic human gastric cancer after orthotopic transplantation of histologically intact tumor tissue in nude mice

Abstract

We have established a metastatic model of human gastric cancer using orthotopic transplantation of histologically intact tissue in nude mice, and have used this model to evaluate the effects of immunochemotherapy using OK-432, 5-fluorouracil (5-FU) and mitomycin C (MMC) against SC-I-NU, a human stomach cancer line. One-quarter or one-half maximum tolerated doses (MTDs) of 5-FU or MMC resulted in a significant reduction of stomach tumor growth, while liver metastases were not reduced, possibly due to suppression of natural killer (NK)-cell activity by both drugs. On the other hand, when combined with OK-432, half MTDs of 5-FU and MMC significantly reduced liver metastases, with synergistic reduction of stomach tumor growth, possibly reflecting a rescue of NK-cell activity by treatment with OK-432. This metastatic model of human stomach cancer shows that locally growing and metastatic tumors may have different chemosensitivities, and provides the opportunity to test both with various treatment regimens.