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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1989 Jul;80(7):670–678. doi: 10.1111/j.1349-7006.1989.tb01695.x

Epidermal Growth Factor Receptor‐mediated Selective Cytotoxicity of Antitumor Agents toward Human Xenografts and Murine Syngeneic Solid Tumors

Harunobu Amagase 1, Masanori Kakimoto 1, Ken Hashimoto 1, Tohru Fuwa 1, Shigeru Tsukagoshi 2
PMCID: PMC5917811  PMID: 2507490

Abstract

Severe toxic side effects of antiproliferative agents limit their clinical usefulness as anti tumor drugs. Recently we observed that the anti tumor efficacy of various anti tumor agents (5‐fluorouracil, tegafur, adriamycin, mitomycin C, cyclophosphamide, and cisplatin) against experimental solid tumors was enhanced by prior or simultaneous administration of human epidermal growth factor (EGF). However, coadministration of EGF did not enhance the toxicity of anti tumor agents as measured by LD50 and body weight loss. The above selective potentiation of efficacy of the anti tumor agents by human EGF can be characterized as follows. In a dose‐dependent manner, human EGF enhanced the efficacy of an antitumor agent (5‐FU) treatment against human epidermoid carcinoma A431 transplanted sc in atliymic nude mice [ED50=2.9 (0.2–49.7, 95% confidence interval) μg/kg, sc]. Various degrees of enhancement were also observed against other experimental tumors transplanted sc. The degrees of enhancement were directly proportional to the numbers of human EGF binding sites present on tumor cell plasma membrane (threshold of binding site density=1.5×103 sites/cell) using 5‐FU or cisplatin as an anti tumor agent, thus suggesting that the binding of EGF to the receptors on tumor cells is an essential process in enhancing the susceptibility of tumor cells to anti tumor agents. Normal cells including intestinal epithelial and bone marrow cells are endowed with fewer EGF binding sites (less than 103 sites/cell). This may explain partially the absence of EGF‐enhanced cytotoxicity by antitumor agents toward normal cells.

Keywords: Human EGF, Adjuvant chemotherapy, Human tumor inhibition, Biological response modifier, EGF receptor

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