CTBP2 contributes to cisplatin resistance in lung adenocarcinoma by inhibiting generation of reactive oxygen species

Mingqun Wang; Linshan Shi; Shiming Fan; Chunsheng Hu

doi:10.21037/tcr-23-2135

CTBP2 contributes to cisplatin resistance in lung adenocarcinoma by inhibiting generation of reactive oxygen species

Transl Cancer Res. 2024 Apr 30;13(4):1695-1706. doi: 10.21037/tcr-23-2135. Epub 2024 Apr 15.

Authors

Mingqun Wang¹, Linshan Shi², Shiming Fan³, Chunsheng Hu^{2

4}

Affiliations

¹ Department of Pharmacy, Changning County Hospital of Traditional Chinese Medicine, Yibin, China.
² College of Pharmacy (International Academy of Targeted Therapeutics and Innovation), Chongqing University of Arts and Sciences, Chongqing, China.
³ Department of Respiratory and Critical Care Medicine, Changning County Hospital of Traditional Chinese Medicine, Yibin, China.
⁴ Chongqing Key Laboratory of Chinese Medicine & Health Science, Chongqing Academy of Chinese Materia Medica, Chongqing, China.

Abstract

Background: Cisplatin (CP) is commonly used for the initial treatment of lung adenocarcinoma (LUAD). Resistance to CP has long been recognized as a significant obstacle to achieving improved therapeutic outcomes. Nevertheless, the intricate molecular mechanisms underlying the phenomenon remain incompletely understood.

Methods: The present study utilized the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to conduct an analysis of the expression of C-terminal binding protein 2 (CTBP2) in LUAD. The correlation between CTBP2 expression and survival data was investigated by the Kaplan-Meier (K-M) plotter. Subsequently, the roles of CTBP2 in CP resistance were explored by analyzing cell viability, cell apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) in CP-resistant cells (A549/DDP).

Results: Our data indicated that the CTBP2 expression in LUAD exhibited a significant increase compared to the non-malignant tissues. CTBP2 overexpression showed a correlation to poor survival. CTBP2 knockdown significantly enhanced cell sensitivity to CP in A549/DDP cells. The underlying mechanism is related to promoting ROS production and decreasing MMP after CP treatment.

Conclusions: CTBP2 expression has been identified as a novel biomarker for resistance to CP, and its downregulation has been found to enhance sensitivity to CP. Therefore, CTBP2 can serve as a predictor related to CP resistance and a viable therapeutic target for CP resistance in LUAD.

Keywords: C-terminal binding protein 2 (CTBP2); bioinformatics analysis; cisplatin resistance; lung adenocarcinoma (LUAD); reactive oxygen species (ROS).