Inhibitory effect of anti-epidermal growth factor receptor antibody on a human gastric cancer.
BACKGROUND
Blockading the putative epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha)/EGF receptor autocrine pathway with anti-EGF receptor monoclonal antibody (MoAb) might prevent the growth of tumor.


METHODS
The present study was designed to examine the effect of MoAb 528 on the growth of an EGF receptor which was hyperproducing human gastric cancer cells in vitro and in vivo.


RESULTS
Treatment with MoAb 528 inhibited the growth of cultured cells in a dose-dependent manner. Twenty micrograms of MoAb 528 given intraperitoneally after inoculation of 1 x 10(6) cells and 200 micrograms of the MoAb 528 given after inoculation of 1 x 10(7) cells to athymic mice inhibited the growth of the xenograft. Twenty micrograms of MoAb 528 from a miniosmotic pump, which releases its contents over 2 weeks, also prevented the growth of the xenograft when the treatment was started on the day after tumor inoculation. However, no inhibitory effect was observed when the treatment was started 3 weeks after inoculation. The binding capacity of 125I-EGF on the MoAb treated tumors was diminished in comparison with control tumors.


CONCLUSIONS
The results suggest that MoAb 528 blocks the EGF or TGF-alpha/EGF receptor signal pathway, resulting in the inhibition of cancer cell growth. This MoAb 528 may therefore be an effective antitumor agent against human gastric cancer that shows expression of the EGF receptor.
Teramoto
T
T
First Department of Surgery, Nippon Medical School, Tokyo, Japan.
Onda
M
M
Tokunaga
A
A
Asano
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011869:Radioligand Assay; D013274:Stomach Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000648:ultrastructure*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors