Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB

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  • Wang, Cun-Yu
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Cusack, James C., Jr.
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Liu, Rong
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Baldwin, Albert
Abstract
  • Programmed cell death (apoptosis) seems to be the principal mechanism whereby anti-oncogenic therapies such as chemotherapy and radiation effect their responses. Resistance to apoptosis, therefore, is probably a principal mechanism whereby tumors are able to overcome these cancer therapies. The transcription factor NF-κB is activated by chemotherapy and by irradiation in some cancer cell lines. Furthermore, inhibition of NF-κB in vitro leads to enhanced apoptosis in response to a variety of different stimuli. We show here that inhibition of NF-κB through the adenoviral delivery of a modified form of IκBα, the inhibitor of NF-κB, sensitizes chemoresistant tumors to the apoptotic potential of TNFκ and of the chemotherapeutic compound CPT-11, resulting in tumor regression. These results demonstrate that the activation of NF-κB in response to chemotherapy is a principal mechanism of inducible tumor chemoresistance, and establish the inhibition of NF-κB as a new approach to adjuvant therapy in cancer treatment.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Nature Medicine
Journal volume
  • 5
Journal issue
  • 4
Page start
  • 412
Page end
  • 417
Language
  • English
Version
  • Postprint
ISSN
  • 1546-170X

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