We assessed the antiproliferative effects of human recombinant interferon-alpha; 2a (IFNalpha; 2a) and 13-c/s-retinoic acid (13c/s-RA) on two human melanoma cell lines (JR8 and M14). Both cell lines showed a very modest sensitivity to IFNalpha; 2a and 13c/s-RA as single agents. In JR8 cells, the combination of the two compounds consistently produced simple additive effects. In contrast, different effects of the combination were recorded in the M14 cell line depending on the treatment schedule. Specifically, an additive interaction was observed when IFNalpha; 2a and 13c/s-RA were given in sequence, independently of the order of drug administration, whereas a supra-additive antiproliferative effect was seen when cells were simultaneously exposed to the two drugs. Exposure to 1000 IU/ml IFNalpha; 2a markedly increased the nuclear expression of signal transducers and activators of transcription (STAT) proteins in both cell lines. By itself 10 micro;M 13c/s-RA did not affect STAT protein expression or modify the extent of activation of such proteins by IFNalpha; 2a. Results from our study showed an enhancement of the antiproliferative activity of IFNalpha; 2a and 13c/s-RA when given in combination and suggest that such an enhancement is not mediated by a concomitant effect of 13c/s-RA on STAT protein activation. copy; 1998 Rapid Science Ltd.
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