Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB Public Deposited
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- Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology, School of Dentistry, Department of Endodontics, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
Cusack, James C., Jr.
- Affiliation: School of Medicine, Department of Surgery, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
- ORCID: https://orcid.org/0000-0003-1246-1349
- Affiliation: College of Arts and Sciences, School of Medicine, Curriculum in Genetics and Molecular Biology, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, Department of Biology
- Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
- 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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|Control of inducible chemoresistance_Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB.pdf||2019-05-03||Public||