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...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1996-03, Vol.56 (6), p.1303-1308
Main Authors: LI-FEN LEE, SCHUERER-MALY, C.-C, LOFQUIST, A. K, VAN HAAFTEN-DAY, C, TING, J. P.-Y, WHITE, C. M, MARTIN, B. K, HASKILL, J. S
Format: Article
Language:English
Subjects:
Administration, Topical
Anti-Inflammatory Agents - pharmacology
Antineoplastic agents
Antineoplastic Agents, Phytogenic - pharmacology
Biological and medical sciences
Cell Division - drug effects
Colonic Neoplasms - metabolism
Dimethyl Sulfoxide - pharmacology
Female
General aspects
Humans
Interleukin-8 - biosynthesis
Medical sciences
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Paclitaxel - pharmacology
Pharmacology. Drug treatments
RNA, Messenger - biosynthesis
Transcription, Genetic
Tumor Cells, Cultured
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0008-5472
1538-7445