GOLPH3 inhibition overcomes cisplatin resistance by restoring the glutathione/reactive oxygen species balance in the A549 non‑small cell lung cancer cell line

Wei,Qiongying; Lin,Jinquan; Lin,Zhuangbin; Yu,Nanding; Wu,Yingxiao; Tan,Xuexue; Xue,Dan

doi:10.3892/or.2024.8829

GOLPH3 inhibition overcomes cisplatin resistance by restoring the glutathione/reactive oxygen species balance in the A549 non‑small cell lung cancer cell line

Authors:
- Qiongying Wei
- Jinquan Lin
- Zhuangbin Lin
- Nanding Yu
- Yingxiao Wu
- Xuexue Tan
- Dan Xue
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Affiliations: Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Trauma Center and Emergency Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China, Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
Published online on: October 18, 2024 https://doi.org/10.3892/or.2024.8829
Article Number: 170
Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cisplatin resistance is common in non‑small cell lung cancer (NSCLC); however, the molecular mechanisms remain unclear. The present study aimed to identify a new function of Golgi phosphoprotein 3 (GOLPH3) in NSCLC‑associated cisplatin resistance. Using A549 human NSCLC cells and the cisplatin‑resistant variant, stable cell lines with GOLPH3 knockdown or overexpression were established using lentiviral vectors. Through Cell Counting Kit‑8 and EdU assays, it was revealed that knockdown of GOLPH3 significantly enhanced cisplatin sensitivity in NSCLC cells. Specifically, flow cytometric analysis showed that GOLPH3 knockdown promoted apoptosis and G₂‑phase cell cycle arrest in A549 cells. Mechanistically, intracellular reactive oxygen species (ROS) and glutathione (GSH) levels were measured using assay kits, and it was demonstrated that GOLPH3 knockdown decreased intracellular GSH levels, and further attenuated intracellular cisplatin efflux and GSH/ROS imbalance. In addition, tumor‑sphere formation assays verified that GOLPH3 knockdown mitigated the stem cell‑like phenotype of NSCLC cells. In conclusion, the present findings indicated the relevance of GOLPH3 in NSCLC‑associated cisplatin resistance, and thus targeting GOLPH3 may be developed into a combination therapy to overcome cisplatin resistance.

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