Influence of L-methionine-deprived total parenteral nutrition with 5-fluorouracil on gastric cancer and host metabolism

AIM To investigate the influence of L-methionine-deprived total parenteral nutrition with 5-FU on gastric cancer and host metabolism. METHODS N-methyl-N'-nitro-nitrosoguanidine ( MNNG) induced gastric cancer r ats were randomly divided into four groups: Met-containing TPN group ( n = 11), Met-deprived TPN group (n = 12), Met-containing TPN + 5-FU group ( n = 11) and Met-deprived TPN + 5-FU group (n = 12). Five rats in each group we re sacrificed after 7 days of treatment and the samples were taken for exam ination. The remaining rats in each group were then fed separately with nor mal diet after the treatment until death, the life span was noted. RESULTS The tumors were enlarged in Met-containing group and shrank in Met- deprived group markedly after the treatment. The DNA index (DI) of tumor ce lls and the body weight (BW) of rats had no significant change in the two g roups, however, the ratio of tumor cells' S phase was increased. The ratio of G2M phase went up in Met-containing group, but down in Met-deprived grou p. In the other two groups that 5-FU was added, the BW of rats, and the dia meter of tumors, the Di of tumor cells, the S and G2M phase ratio of tumor cells were all decreased, particularly in Met-deprived plus 5-FU group. Pat hological examination revealed that the necrotic foci of the tumor tissue i ncreased after Met-deprived TPN treatment, and the nucleoli of tumor cells enlarged. In -MetTPN + 5-FU group, severe nuclear damage was also found by karyopyknosis and karyorrhexis, meanwhile there was slight degeneration in some liver and kidney cells. The serum free Met and Cysteine decreased mark edly (P < 0.001), while other amino acids, such as serum free serine and gl utamine increased significantly (P < 0.005). All the rats died of multiple organ failure caused by cancer metastasis. The average survival time was 18 .6 days in Met-containing TPN group, 31 days in Met-deprived TPN group, 27. 5 days in Met-containing TPN + 5-FU group, and 43 days in Met-deprived TPN + 5-FU group (P < 0.05). CONCLUSION Met-deprived TPN causes methionine starvation of tumor cells, an d can enhance the anti-tumor effect of 5-FU and prolong the life span of ga stric cancer-bearing rats.