Overexpression of OCT4 is associated with gefitinib resistance in non-small cell lung cancer

Bin Li1, Zhouhong Yao1, Yunyan Wan1

  • 1Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong, China, 250021.

Oncotarget
|November 7, 2016
PubMed

Insights

Octamer-binding transcription factor 4 (OCT4) is highly expressed in non-small cell lung cancer (NSCLC) and contributes to gefitinib resistance. Reducing OCT4 enhances apoptosis and decreases proliferation in NSCLC cells treated with gefitinib.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs) are first-line treatments for non-small cell lung cancer (NSCLC).
  • Therapeutic resistance to TKIs significantly limits their clinical efficacy in NSCLC treatment.
  • The role of specific molecular markers in mediating TKI resistance remains an area of active investigation.

Purpose of the Study:

  • To investigate the role of Octamer-binding transcription factor 4 (OCT4) in the development of resistance to EGFR-targeted TKIs in NSCLC.
  • To determine the correlation between OCT4 expression levels and TKI sensitivity in NSCLC cells.
  • To explore the potential of targeting OCT4 to overcome gefitinib resistance.

Main Methods:

  • Quantitative analysis of OCT4 expression in NSCLC tissues versus adjacent non-tumourous tissues.
  • In vitro knockdown of OCT4 expression in NSCLC cell lines.
  • Assessment of cell proliferation and apoptosis following OCT4 knockdown and gefitinib treatment.

Main Results:

  • A statistically significant difference in OCT4 expression was observed between NSCLC and non-tumourous tissues.
  • Knockdown of OCT4 in NSCLC cells led to decreased cell proliferation.
  • Reduced OCT4 expression potentiated gefitinib-induced apoptosis in NSCLC cells.

Conclusions:

  • OCT4 expression is significantly different in NSCLC compared to normal tissues.
  • OCT4 plays a crucial role in promoting cell proliferation and conferring resistance to gefitinib in NSCLC.
  • Targeting OCT4 may represent a viable strategy to enhance the efficacy of gefitinib therapy for NSCLC patients.