GBP2 enhances paclitaxel sensitivity in triple‑negative breast cancer by promoting autophagy in combination with ATG2 and inhibiting the PI3K/AKT/mTOR pathway

Zhang,Weidan; Tang,Xin; Peng,Yang; Xu,Yingkun; Liu,Li; Liu,Shengchun

doi:10.3892/ijo.2024.5622

GBP2 enhances paclitaxel sensitivity in triple‑negative breast cancer by promoting autophagy in combination with ATG2 and inhibiting the PI3K/AKT/mTOR pathway

Authors:
- Weidan Zhang
- Xin Tang
- Yang Peng
- Yingkun Xu
- Li Liu
- Shengchun Liu
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Affiliations: Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Rehabilitation Medicine, The People's Hospital of Tongliang, Chongqing 402560, P.R. China
Published online on: February 6, 2024 https://doi.org/10.3892/ijo.2024.5622
Article Number: 34
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemoresistance is a major challenge in treating triple‑negative breast cancer (TNBC); chemotherapy remains the primary approach. The present study aimed to elucidate the role of guanylate‑binding protein 2 (GBP2) in activating autophagy in TNBC and its impact on the sensitivity of TNBC cells to paclitaxel (PTX). Transfection with lentivirus was performed to establish TNBC cell lines with stable, high GBP2 expression. The mRNA and protein levels of GBP2 expression were evaluated utilizing reverse transcription‑quantitative PCR and western blotting, respectively. Autophagy in TNBC cells was evaluated using immunoblotting, transmission electron microscopy and fluorescence microscopy. The PI3K/AKT/mTOR pathway proteins and their phosphorylation were detected by immunoblotting, and fluorescence co‑localization analysis was performed to evaluate the association between GBP2 and autophagy‑related protein 2 (ATG2). BALB/c NUDE mice were subcutaneously injected with GBP2 wild‑type/overexpressing MDA‑MB‑231 cells. Low GBP2 expression was detected in TNBC, which was associated with a poor prognosis. Overexpression of GBP2 suppressed cell growth, and especially enhanced autophagy in TNBC. Forced expression of GBP2 significantly increased the PTX sensitivity of TNBC cells, and the addition of autophagy inhibitors reversed this effect. GBP2 serves as a prognostic marker and exerts a notable inhibitory impact on TNBC. It functions as a critical regulator of activated autophagy by co‑acting with ATG2 and inhibiting the PI3K/AKT/mTOR pathway, which contributes to increasing sensitivity of TNBC cells to PTX. Therefore, GBP2 is a promising therapeutic target for enhancing TNBC treatment.

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