Transcriptomic profiling of autophagy and apoptosis pathways in liver cancer cells treated with a new tyrosine kinase inhibitor PD161570

He,Xingxing; Liu,Jianping; Zhang,Yulian; Xie,Bushan

doi:10.3892/mmr.2025.13540

Transcriptomic profiling of autophagy and apoptosis pathways in liver cancer cells treated with a new tyrosine kinase inhibitor PD161570

Authors:
- Xingxing He
- Jianping Liu
- Yulian Zhang
- Bushan Xie
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Affiliations: Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Jiangxi Provincial Key Laboratory of Digestive Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: April 16, 2025 https://doi.org/10.3892/mmr.2025.13540
Article Number: 175
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer is the third most lethal and prevalent cancer in the Asia‑Pacific regions. Despite the use of tyrosine kinase inhibitors as first‑ and second‑line therapies, the overall survival rate for advanced liver cancer remains dismal and has not improved over the past decade. The present study, through high‑throughput screening, identified and demonstrated that PD161570, a new tyrosine kinase inhibitor, inhibited cell growth and proliferation in liver cancer cells. Mechanistically, PD161570 induced autophagy and enhanced autophagic flux in an autophagy‑related gene (ATG5)‑dependent and mammalian target of rapamycin kinase‑independent manner. Furthermore, when combined with chloroquine treatment, PD161570 not only suppressed cell proliferation but also increased cell apoptosis due to autophagy inhibition. RNA sequencing analysis revealed 1,121 differentially expressed genes in liver cancer cells following PD161570 treatment under autophagy inhibition via ATG5 knockdown. Notably, key molecules involved in autophagy (such as Damage Regulated Autophagy Modulator 1) and apoptosis regulators (including HRK, CTSS, BIRC3, BBC3, DDIT3 and GADD45B), were identified. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), demonstrated enrichment in apoptotic and cell death signaling pathways, highlighting the critical role of the mitogen‑activated protein kinases signaling pathway. In conclusion, PD161570 elicited an ATG5‑dependent autophagic process in liver cancer cells, while simultaneously enhancing apoptosis under conditions of autophagy inhibition.

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