Anti-Gastrins Antiserum Combined with Lowered Dosage Cytotoxic Drugs to Inhibit the Growth of Human Gastric Cancer SGC7901 Cells in Nude Mice

摘要

The objective of this study was to determine the effect of anti-gastrin antiserum in combination with varied dosages of cytotoxic drugs (5-Fluorouracil (5FU) + Cisplatin (CDDP)) in vivo growth of the human gastric cancer cell-line, SGC-7901, which expressed cholecystokininB/gastrin receptors and secreted gastrin. The anti-gastrin antiserum was obtained by immunizing rabbits using a novel immunogen vaccine, which was composed of the common amino-terminal portion of human carboxy-amidated gastrin-17 (G17) and glycine-extended gastrin-17 (gly-G17) and the common carboxy-terminal portion of progastrin (in a 50:50 mixture) all covalently linked to tetanus toxoid (TT) by specific peptide spacers. The antiserum neutralized both G17 and gly-G17 by enzyme-linked immunosorbent assay (ELISA), and a synthetic progastrin peptide, as well, using an E. coli expressed his-tagged progastrin.The tumor was implanted subcutaneously into the backside of BALB/c nude mice, and the combination antibody-drug treatment using low dose combination chemotherapy had significantly reduced median tumor volumes (62% reduction; p =0.0018) and tumor weights (53% reduction; p =0.0062) when compared to the conventional high dose chemotherapy treated control mice that had a corresponding similar reductive effect, using just the two standard cytotoxic drugs alone; namely by reducing the tumor volumes (65%; p =0.0016) and tumor weights (59% reduction; p=0.0033). Importantly, the immunological treatment had little of the toxicities and side-effects of the full chemotherapy doses alone, which was effected by using a significant decrease in the dosage of chemotherapeutic drugs, while maintaining the same level of efficacy at reduction of tumor growth.