Cancer Immunology, Immunotherapy

, Volume 49, Issue 2, pp 78–84

Paclitaxel up-regulates interleukin-8 synthesis in human lung carcinoma through an NF-κB- and AP-1-dependent mechanism

  • Timothy S. Collins
  • Li-Fen Lee
  • Jenny P.-Y. Ting
ORIGINAL ARTICLE

DOI: 10.1007/s002620050605

Cite this article as:
Collins, T., Lee, LF. & Ting, JY. Cancer Immunol Immunother (2000) 49: 78. doi:10.1007/s002620050605

Abstract

 Lung cancer is a leading cause of cancer-related death in the United States. For this reason we chose to study the specific cellular effects that one chemotherapeutic agent, paclitaxel, has on lung carcinoma. In addition to its known mechanism of action, which is to stabilize microtubules, paclitaxel has been shown to have other interesting and relevant cellular effects. In this report, we demonstrate that a subset of human lung carcinoma cell lines respond to paclitaxel treatment with an up to a fivefold increase in the production of interleukin-8 (IL-8). We demonstrate that this increased production is specific to IL-8 but not to other chemokines, and is both dose- and time-dependent. Increased IL-8 mRNA is seen as early as 45 min with a peak at 4 h after paclitaxel treatment. This increase in mRNA is due to transcriptional activation because actinomycin D treatment blocked the increase. Paclitaxel also activates the mitogen-activated protein kinase family member, JNK1, in dose-dependent fashion. IL-8 enhancement is completely abolished with the use of an inhibitor of NF-κB, the super-repressor IκB. Similar results were obtained upon the inhibition of AP-1 activation with the MEK1/2 inhibitor, U0126. By gaining a better understanding of the differences in cellular response to paclitaxel chemotherapy, these findings might lead to either improved patient selection or to the development of adjuvant therapy targeted at specific-cell signaling proteins.

Key words LungChemokinesSignal transductionTranscription factors

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Timothy S. Collins
    • 1
  • Li-Fen Lee
    • 2
  • Jenny P.-Y. Ting
    • 3
  1. 1.University of North Carolina Lineberger Comprehensive Cancer Center, Department of Surgery, Chapel Hill, NC 27599-7295, USAUS
  2. 2.University of North Carolina Lineberger Comprehensive Cancer Center, Department of Biology, University of North Carolina, Chapel Hill, NC 27599-7295, USAUS
  3. 3.University of North Carolina Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, Campus Box 7295, UNC-Chapel Hill, Chapel Hill, NC 27599-7295, USAUS