TAXOL-DEPENDENT TRANSCRIPTIONAL ACTIVATION OF IL-8 EXPRESSION IN A SUBSET OF HUMAN OVARIAN-CANCER

Taxol is important in the treatment of both primary and drug-resistant ovarian cancer. Although Taxol is known to stabilize microtubules and block cell mitosis, the effectiveness of this drug exceeds that of ot her antimitotic agents, suggesting it may have an additional mode of a ction. Stimulated by murine macrophage studies indicating cytokine ind uction by Taxol, we have investigated proinflammatory cytokine express ion in a series of cell lines and recent explants of human ovarian can cer. Taxol induced secretion of interleukin (IL) 8 but not IL-6, IL-1 alpha, or IL-1 beta in 4 of 10 samples. Induction was dependent on tra nscriptional activation, and, in contrast to murine macrophage studies , was apparently independent of an active lipopolysaccharide signaling pathway, Confluent cultures secreted as much IL-8 as proliferating ce lls. Taxol did not induce IL-8 in breast carcinoma, endometrial stroma l, or T-lymphocyte or monocyte cultures. We propose that the local exp ression of this chemokine in vivo may elicit a host response similar i n effectiveness to that of cytokine gene therapy. These data are the f irst to suggest that a chemotherapeutic agent may have a direct effect on transcription of cytokine and/or growth factor genes in ovarian ca ncer, and that this effect may not be restricted to proliferating tumo r cells.