Work

Paeoniae radix overcomes resistance to EGFR-TKIs via aurora B pathway suppression in lung adenocarcinoma

Year: 2024

Type: article

Abstract: Targeted therapies using epidermal growth factor receptor (EGFR) inhibitors have markedly improved survival rates and quality of life for patients with EGFR-mutant lung adenocarcinoma (LUAD). Despite these advancements, resistance to EGFR inhibitors remains a significant challenge, limiting the overall effectiveness of the treatment. This study explored the synergistic effects of combining Paeoniae Radix (PR) with first-generation EGFR-tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, to overcome this resistance. Transcriptomic analysis of EGFR-mutant LUAD cell lines revealed that PR treatment could potentially reverse the gene signatures associated with resistance to EGFR-TKIs, primarily through the suppression of the Aurora B pathway. Experimental validation demonstrated that combining PR with erlotinib and gefitinib enhanced drug responsiveness by inhibiting Aurora kinase activity and inducing apoptosis in LUAD cells. Additionally, gene expression changes confirmed these combined effects, with the suppression of the Aurora B pathway and upregulation of the apoptotic pathway, which was accompanied by increased expression of multiple pro-apoptotic genes. Our findings contribute to the development of natural product-based therapeutic strategies to mitigate drug resistance in LUAD.

Source: Life Sciences

DOI: 10.1016/j.lfs.2024.123097

Authors: Heerim Yeo, Haeseung Lee, Sang-Min Park, Han Na Kang

Institutions: Chungnam National University, Pusan National University, Korea Institute of Oriental Medicine

Language: English

Topic: Lung Cancer Treatments and Mutations

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430