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GdX Inhibits the Occurrence and Progression of Breast Cancer by Negatively Modulating the Activity of STAT3

Overview
Journal Cancer Biol Ther
Specialties Oncology
Pharmacology
Date 2024 Nov 2
PMID 39487760
Authors
Zhilin Chen
Lu Xu
Shibin Lin
Hongjun Huang
Qing Long
Jiwei Liu
Affiliations
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Abstract

Aim: To elucidate the biological functionality and regulatory mechanisms of GdX in breast cancer (BC).

Methods: The examination of GdX expression in human BC tissues and cell lines was conducted through immunohistochemical (IHC) and Western blot. Cell proliferation capacity was assessed via the CCK-8 and colony formation assay, while cell migration was determined through the wound healing assay. The expression levels of BCL-XL, Cyclin D1, and C-myc gene were quantified using RT-qPCR and Western blot. In vivo tumor growth was evaluated in nude mice xenografted with MDA-MB-231 cells overexpressing GdX, and a mouse model with GdX-deficient BC was established to observe the impact of GdX on BC formation and metastasis. Dual-luciferase reporter assay and immunofluorescence were employed to confirm the interaction between GdX and STAT3. Western blot was employed to validate the influence of GdX overexpression on the phosphorylation process of STAT3.

Results: GdX exhibited low expression in the cancer tissues of BC patients and cell lines. MDA-MB-231 and MCF-7 cells overexpressing GdX displayed a notable reduction in proliferation and diminished migratory capabilities, accompanied by downregulated mRNA and protein expression of BCL-XL, Cyclin D1, and C-myc. In the xenograft mouse model, heightened GdX expression correlated with a decelerated in vivo tumor growth. Furthermore, in mice deteleing GdX, both the quantity and weight of tumors increased, along with evident pulmonary metastasis. Mechanistically, STAT3 emerged as a downstream target gene of GdX.

Conclusions: GdX exerts its inhibitory effects on the initiation and progression of BC by negatively modulating the phosphorylation of STAT3.

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