Evaluation of the STAT3 inhibitor GLG‑302 for the prevention of estrogen receptor‑positive and ‑negative mammary cancers

  • Authors:
    • Robert H. Shoemaker
    • Jennifer T. Fox
    • Margaret M. Juliana
    • Fariba L. Moeinpour
    • Clinton J. Grubbs
  • View Affiliations

  • Published online on: July 4, 2019     https://doi.org/10.3892/or.2019.7219
  • Pages: 1205-1213
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Abstract

Signal transducer and activator of transcription 3 (STAT3) plays a key role in the transformation of normal cells to cancerous cells. Although inhibitors of STAT3 have been shown to suppress the growth of multiple cancer types in vitro and in vivo, such agents are of particular interest for the prevention of breast cancer, which affects over 200,000 women and claims more than 40,000 lives in the United States each year. In the present study, we employed the MMTV/Neu transgenic mouse model, which develops estrogen receptor (ER)‑negative, Neu‑overexpressing tumors, and the Sprague‑Dawley (SD) rat model, which develops ER‑positive tumors upon exposure to the carcinogen 7,12‑dimethylbenz[a]anthracene (DMBA), to test the efficacy of the STAT3 inhibitor GLG‑302 in the prevention of mammary cancer. Orally administered GLG‑302 and its trizma salt derivative reduced mammary cancer incidence, multiplicity, and tumor weights in female MMTV/Neu mice, and GLG‑302 reduced tumor multiplicity and weights in female DMBA‑treated rats. Consistent with the mechanism of action of STAT3 inhibitors, the reductions in mammary tumors were correlated with decreases in STAT3 phosphorylation and cell proliferation. These data suggest that GLG‑302 is a novel agent with potential for prevention of mammary cancer and support the further development of STAT3 inhibitors for this cause.
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September-2019
Volume 42 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Shoemaker RH, Fox JT, Juliana MM, Moeinpour FL and Grubbs CJ: Evaluation of the STAT3 inhibitor GLG‑302 for the prevention of estrogen receptor‑positive and ‑negative mammary cancers. Oncol Rep 42: 1205-1213, 2019
APA
Shoemaker, R.H., Fox, J.T., Juliana, M.M., Moeinpour, F.L., & Grubbs, C.J. (2019). Evaluation of the STAT3 inhibitor GLG‑302 for the prevention of estrogen receptor‑positive and ‑negative mammary cancers. Oncology Reports, 42, 1205-1213. https://doi.org/10.3892/or.2019.7219
MLA
Shoemaker, R. H., Fox, J. T., Juliana, M. M., Moeinpour, F. L., Grubbs, C. J."Evaluation of the STAT3 inhibitor GLG‑302 for the prevention of estrogen receptor‑positive and ‑negative mammary cancers". Oncology Reports 42.3 (2019): 1205-1213.
Chicago
Shoemaker, R. H., Fox, J. T., Juliana, M. M., Moeinpour, F. L., Grubbs, C. J."Evaluation of the STAT3 inhibitor GLG‑302 for the prevention of estrogen receptor‑positive and ‑negative mammary cancers". Oncology Reports 42, no. 3 (2019): 1205-1213. https://doi.org/10.3892/or.2019.7219