Overexpression of OCT4 is associated with gefitinib resistance in non-small cell lung cancer
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Updated: Mar 12, 2026

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Bin Li1, Zhouhong Yao1, Yunyan Wan1
1Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong, China, 250021.
Abstract:
Epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs) have emerged as first-line drugs for non-small cell lung cancers (NSCLCs). However, the resistance to TKIs represents the key limitation for their therapeutic efficacy. We found that the difference of OCT4 expression between NSCLC and the adjacent non-tumourous tissues was statistically significant. Knockdown of OCT4 in NSCLC cells could decrease cell proliferation, and potentiate apoptosis induced by gefitinib, suggesting OCT4 may contribute to gefitinib resistance in NSCLC.
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.
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