American Association for Cancer Research
Browse
00085472can111646-sup-s1_pdf_2772k.pdf (2.71 MB)

Supplementary Figure 1 from Inhibition of Neurotensin Receptor 1 Selectively Sensitizes Prostate Cancer to Ionizing Radiation

Download (2.71 MB)
journal contribution
posted on 2023-03-30, 20:44 authored by Nicholas C.K. Valerie, Eli V. Casarez, John O. DaSilva, Marya E. Dunlap-Brown, Sarah J. Parsons, George P. Amorino, Jaroslaw Dziegielewski

PDF file - 2.71MB

History

ARTICLE ABSTRACT

Radiotherapy combined with androgen depletion is generally successful for treating locally advanced prostate cancer. However, radioresistance that contributes to recurrence remains a major therapeutic problem in many patients. In this study, we define the high-affinity neurotensin receptor 1 (NTR1) as a tractable new molecular target to radiosensitize prostate cancers. The selective NTR1 antagonist SR48692 sensitized prostate cancer cells in a dose- and time-dependent manner, increasing apoptotic cell death and decreasing clonogenic survival. The observed cancer selectivity for combinations of SR48692 and radiation reflected differential expression of NTR1, which is highly expressed in prostate cancer cells but not in normal prostate epithelial cells. Radiosensitization was not affected by androgen dependence or androgen receptor expression status. NTR1 inhibition in cancer cell–attenuated epidermal growth factor receptor activation and downstream signaling, whether induced by neurotensin or ionizing radiation, establish a molecular mechanism for sensitization. Most notably, SR48692 efficiently radiosensitized PC-3M orthotopic human tumor xenografts in mice, and significantly reduced tumor burden. Taken together, our findings offer preclinical proof of concept for targeting the NTR1 receptor as a strategy to improve efficacy and outcomes of prostate cancer treatments using radiotherapy. Cancer Res; 71(21); 6817–26. ©2011 AACR.

Usage metrics

    Cancer Research

    Categories

    Keywords

    Cell SignalingAutocrine-paracrine signalingDrug MechanismsDrug TargetsCell surface receptor drug targetsEndocrinologyGenitourinary CancersProstate cancerImagingSmall animal imagingRadiation OncologyExperimental radiotherapeuticsRadioprotectors and radiosensitizersRadiobiologyRadiation-activated signaling pathways

    Licence

    CC BY

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC