Receptor binding of epidermal growth factor in cultured human choriocarcinoma cell lines: effects of actinomycin-D and methotrexate.

Abstract

Binding of epidermal growth factor (EGF) to its receptor was evaluated in the four cultured choriocarcinoma cell lines BeWo, NaUCC-1, NaUCC-2, and NaUCC-3. Also, the effect of the anti-tumor drugs actinomycin-D (Act-D) and methotrexate (MTX) on the EGF receptor binding was investigated in these cell lines. Incubation of these cells with [125I]EGF at 37 degrees C resulted in a higher binding than that at 22 degrees C or at 4 degrees C. These bindings were saturable during 30- to 60-min incubation, and were specific and reversible. Scatchard analysis showed that the maximal number of receptor binding sites was 2.89 X 10(3)/cell in BeWo cells, 2.04 X 10(3)/cell in NaUCC-1 cells, 1.84 X 10(3)/cell in NaUCC-2 cells, and 1.01 X 10(3)/cell in NaUCC-3 cells. Preincubation with Act-D or MTX for 24 hr decreased the number of receptor binding sites (26%-53%) and slightly increased the receptor binding affinities. Combination of the two drugs resulted in a further diminution of EGF receptor binding sites in BeWo, NaUCC-1, and NaUCC-3 cells, respectively, but reversed the Act-D effect in NaUCC-2 cells. These results indicated that choriocarcinoma tissue is rich in EGF receptors, that the anti-tumor drugs Act-D and MTX diminish the receptor binding sites in the tissue, and suggest that MTX might induce a drug resistance to Act-D in some choriocarcinoma tissue.