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 other antimitotic agents, suggesting it may have an additional mode of action. Stimulated by murine macrophage studies indicating cytokine induction by Taxol, we have investigated proinflammatory cytokine expression in a series of cell lines and recent explants of human ovarian cancer. Taxol induced secretion of interleukin (IL) 8 but not IL-6, IL-1alpha, or IL-1beta in 4 of 10 samples. Induction was dependent on transcriptional 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 cells. Taxol did not induce IL-8 in breast carcinoma, endometrial stromal, or T-lymphocyte or monocyte cultures. We propose that the local expression of this chemokine in vivo may elicit a host response similar in effectiveness to that of cytokine gene therapy. These data are the first to suggest that a chemotherapeutic agent may have a direct effect on transcription of cytokine and/or growth factor genes in ovarian cancer, and that this effect may not be restricted to proliferating tumor cells.
Lee
L F
LF
Department of Biology, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill 27599-7295, USA.
Schuerer-Maly
C C
CC
Lofquist
A K
AK
van Haaften-Day
C
C
Ting
J P
JP
White
C M
CM
Martin
B K
BK
Haskill
J S
JS
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D016209:Interleukin-8; D012333:RNA, Messenger; D017239:Paclitaxel; D004121:Dimethyl Sulfoxide