We have studied the effects of interferon (IFN)-alpha, beta, and gamma in vitro on the growth and invasive potential of human melanoma SK-MEL-118 cells. The antiproliferative effects of IFNs were assessed by a quantitative regrowth assay in which cells were treated with IFNs at concentrations of 10(2), 10(3) or 10(4) IU/ml for 3 days (until day 4) and then further incubated without IFNs for 7 days (until day 11). The growth inhibitory effect of each IFN on melanoma cells was dose- and time-dependent. Among these three types of IFNs, however, IFN-beta exerted the strongest inhibitory effect on cell growth. To assess the anti-invasive effect of each IFN on melanoma cells, we employed an in vitro assay system using matrigel-coated Transwell chambers. When cells were treated with 10(2), 10(3), or 10(4) IU/ml of the three types of IFNs for 24 hours, the amount of tritiated thymidine incorporated into melanoma cells were treated for 24 hours with 10(4) IU/ml of IFN-beta or gamma prior to the assay, the number of cells that invaded the filter decreased by 40%; this decrease was only 10% with the same amount of IFN-alpha. Simultaneous addition of IFNs during the invasion assay was not effective in any combination. Only when the cells were pretreated with IFNs, antiinvasive effects against melanoma cells were exerted. IFN-alpha was less inhibitory than IFN-beta or gamma on proliferation and not at all inhibitory on invasion. Considering both the antiproliferative and antiinvasive effects of IFNs, our results suggest that IFN-beta has the strongest antitumoral effect on human melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of HuIFN-beta on the invasive potential of melanoma cells was studied using an in-vitro model system with Transwell chambers equipped with matrigel-coated polycarbonate filters. When (10(2), 10(3) and 10(4) IU/ml) for 3 days and then grown in medium without HuIFN-beta for another 7 days. On day 7, the proliferation of melanoma cells was inhibited by 77 and 87%, respectively, when cells were treated with 10(2) and 10(4) IU/ml of HuIFN-beta. This antiproliferative effect was dose-dependent and more pronounced on day 11. The effect of HuIFN-beta on the invasive potential of melanoma cells was studied using an in-vitro model system with Transwell chambers equipped with Matrigel-coated polycarbonate filters. When cells were treated with HuIFN-beta (10(2), 10(3) and 10(4) IU/ml) for 24 h, the amount of tritiated thymidine incorporated into cells was increased, indicating that cell growth was not inhibited. However, the number of cells that invaded to the filter decreased significantly by 15-40%. HuIFN-beta did not have an inhibitory effect on the haptotactic migration of melanoma cells. These data indicate that the antiproliferative effect of HuIFN-beta occurs after 24 h and that the direct anti-invasive effect is independent of any effect on proliferation.

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