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

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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Shoemaker RH,Fox JT,Juliana MM,Moeinpour FL,Grubbs CJ

doi

10.3892/or.2019.7219

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

1205-1213

issue

3

eissn

1021-335X

issn

1791-2431

journal_volume

42

pub_type

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