Transfection of ovarian cancer cells with tumor necrosis factor-α (TNF-α) antisense mRNA abolishes the proliferative response to interleukin-1 (IL-1) but not TNF-α

Recombinant interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) can induce endogenous TNF-α mRNA expression and stimulate proliferation of epithelial ovarian cancer cells. In a previous report, proliferation induced by either cytokine could be partially blocked by soluble TNF-α receptor or by neutralizing antibodies against TNF-α. In the present study, we have transfected the ovarian cancer cell line OVCA 432 with vectors that contain the TNF-α gene in the antisense or sense orientation. Antisense-transfected cells showed a 4.5- to 26-fold reduction in IL-1-induced TNF-α secretion. Similarly, the stimulation of [³H]thymidine incorporation by IL-1 but not by TNF-α was blocked by TNF-α antisense transfection. These results are consistent with a model in which the macrophage-derived cytokines IL-1 and TNF-α might stimulate endogenous production of TNF-α that in turn could stimulate proliferation of ovarian cancer cells by autocrine growth regulation.