Response of A431 experimental human solid xenograft to mitomycin C in combination with human epidermal growth factor in mice.
We previously demonstrated that the antitumor efficacy of various antitumor agents such as 5-fluorouracil and cisplatin against experimental solid tumors was enhanced by pre- or simultaneous administration of human epidermal growth factor (hEGF). In the present study, the combined therapy by hEGF and mitomycin C (MMC) as an antitumor agent was studied in A431 solid tumor-bearing mice to determine the dosage schedule of hEGF. When MMC alone was injected intraperitoneally (2 mg/kg) every 7th day to the tumor-bearing mice, tumor weights increased to 2138 +/- 285 mg from 282 +/- 41 mg during 22 d. Tumor weight in every day treatment of hEGF alone for 21 d increased to the same extent in the treatment by MMC alone. On the other hand, the increase of the solid tumor weight in the every day treatment and in the every 7th day treatment of hEGF, in combination with the every 7th day administration of MMC, were as follows; from 282 +/- 41 mg to 1522 +/- 357 mg (71.2 +/- 16.7% of MMC alone) and from 280 +/- 44 mg to 1245 +/- 150 mg (58.2 +/- 7.0% of MMC alone), respectively, demonstrating a greater antitumor potency of MMC in the combination with the every 7th day treatment of hEGF. Both combined therapies did not affect the toxicity of MMC as evaluated by decrease in nontumorous body weight. Single subcutaneous administration of hEGF to A431 tumor-bearing mice caused the decrease of the binding capacity of hEGF to A431 tumor cells by 80% 24 h after the administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Amagase
H
H
Institute for Medical Research, Wakunaga Pharmaceutical Co., Ltd., Hiroshima, Japan.
Tamura
K
K
Hashimoto
K
K
Fuwa
T
T
Murakami
T
T
Yata
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D008937:Mitomycins; D016685:Mitomycin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors