SYNERGISTIC INTERACTION BETWEEN CISPLATIN AND TAMOXIFEN DELAYS THE EMERGENCE OF CISPLATIN RESISTANCE IN HEAD AND NECK-CANCER CELL-LINES

The interaction between cisplatin (cDDP) and tamoxifen (TAM) was evalu ated in the human head and neck squamous-carcinoma cell lines UM-SCC-1 0B and UM-SCC-5. Synergy between cDDP and TAM was demonstrated in the UM-SCC-10B cell line. Concordant with the synergistic effect between c DDP and TAM, the rate of development of resistance to cDDP was delayed when selections were performed in the presence of TAM. However, in th e UM-SCC-5 cell line, TAM was neither synergistic nor did it delay the development of cDDP resistance. The difference with respect to the sy nergistic interaction of cDDP with TAM and the effect on the developme nt of cDDP resistance in the UM-SCC-10B and UM-SCC-5 cell lines was no t related to any significant difference in the accumulation of the cDD P analog [H-3]-cis-dichloro (ethylenediamine)platinum(II) (DEP), drug sensitivity [concentrations inhibiting colony formation by 50% (IC50 v alues) were 6.5 and 7.2 mu M for cDDP and 3.5 and 3.2 mu M for TAM, re spectively], the number of estrogen and progesterone receptors (negati ve in both cell lines), the number of antiestrogen binding sites (404 +/- 85 and 353 +/- 24 fmol/mg protein, respectively), or the affinity of TAM for these binding sites (1.7 and 1.5 nM, respectively). Importa ntly, however, we demonstrated that TAM can delay the emergence of res istance to cDDP in head and neck carcinomas and that this effect is li nked to the nature of the interaction between cDDP and TAM.