Cytosine arabinoside increases the binding of 125I-labelled epidermal growth factor and 125I-transferrin and enhances the in vitro targeting of human tumour cells with anti-(growth factor receptor) mAb.

摘要: We report that cytosine arabinoside (Ara-C), a analogue at low doses causes phenotypical changes on human leukemia cells in vitro and vivo, induces growth inhibition of oropharyngeal cancer KB lung adenocarcinoma A549 cell lines. An increase the number epidermal factor transferrin receptors (EGFR, TrfR) is induced by Ara-C these cells. Maximal EGFR up-regulation occurs 96 h after beginning exposure while maximal TrfR detected 24 later. These effects occur without affinity for their ligands. Two classes EGF-binding sites with aK d 0.055 nM 2.3 respectively, one class transferrin-binding about 4 are both untreated Ara-C-treated [3H]Thymidine uptake clearly stimulated nanomolar concentrations EGF transferrin, whereas [3H]thymidine not increased under conditions where occurs. The enhanced binding paralleled twofold targeting anti-EGFR 108.1 mAb anti-TrfR OKT9 mAb. propose could provide new approach improvement therapeutic index immunoconjugates.