PUBLICATION

Mechanism of etoposide resistance in small cell lung cancer and the potential therapeutic options

Authors
Fan, Y.W., Liu, M.H., Xu, T.J., Fan, R.Y., Xiang, J., Wu, J.Q., He, M.F.
ID
ZDB-PUB-250422-4
Date
2025
Source
Medical oncology (Northwood, London, England)   42: 167167 (Journal)
Registered Authors
Keywords
Drug resistance, Etoposide, Small cell lung cancer, Zebrafish xenograft tumor model
MeSH Terms
  • Zebrafish
  • Cell Line, Tumor
  • Antineoplastic Agents, Phytogenic*/pharmacology
  • Lung Neoplasms*/drug therapy
  • Lung Neoplasms*/genetics
  • Lung Neoplasms*/pathology
  • Animals
  • Etoposide*/pharmacology
  • Etoposide*/therapeutic use
  • Drug Resistance, Neoplasm*/genetics
  • Humans
  • Small Cell Lung Carcinoma*/drug therapy
  • Small Cell Lung Carcinoma*/genetics
  • Small Cell Lung Carcinoma*/pathology
PubMed
40257680 Full text @ Med Oncol
Abstract
Small cell lung cancer (SCLC) is a type of high-grade neuroendocrine malignancy with low gene mutation. Chemotherapy is the major treatment strategy, but long-term clinical application often leads to drug resistance. Etoposide is a first-line drug approved by the US Food and Drug Administration for SCLC treatment, but etoposide-resistance is a problem. In this study, a SCLC cell line with etoposide-acquired resistance, H1048-ER, was constructed through a concentration gradient increasing method, and its resistance to etoposide was investigated in vitro and in a zebrafish model. Through transcriptome sequencing, real-time reverse transcription-quantitative polymerase chain reaction, and bioinformatic analyses of H1048-ER vs. H1048 cells, 51 differentially expressed genes were found to be significantly enriched in "collagen degradation" and "MET/FAK signaling activation in ECM". Among them, six genes (COL11A1, COL26A1, COL4A3, COL4A4, LAMA4, and LAMC1) had strong correlations with the prognosis of lung cancer. They may be key factors in the acquired etoposide resistance of H1048-ER cells. H1048-ER cells showed cross-resistance to cisplatin but were sensitive to doxorubicin and temozolomide. Our study provides novel insights into etoposide resistance in SCLC and affords the potential treatment options after etoposide resistance.
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Sequence Targeting Reagents
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Mapping