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The effect of epidermal growth factor receptor antisense morpholino oligomer on non-small cell lung cancer cell line
Kazuhiro Washio1, Motoi Aoe, Shinichi Toyooka
1Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Abstract:
Overexpression of the epidermal growth factor receptor (EGFR) has been identified as a common component of various cancer types including lung cancer. Recently morpholino oligonucleotides appeared as a promising modification for antisense applications with few toxic effects and their stability. We investigated the effect of EGFR antisense morpholino oligomer on non-small cell lung cancer (NSCLC) cell line by evaluating EGFR mRNA, protein product and cell proliferation. The EGFR antisense morpholino oligomer was designed to target the translation start site in the EGFR mRNA. The four base-mismatch morphlino oligomer was designed as a control for EGFR antisense morpholino oligomer. These morpholino oligomers were introduced into NCI-H125 cell line which showed overexpression of EGFR. The EGFR mRNA and protein expression were quantified by real time RT-PCR and ELISA, respectively. The significant repression in both EGFR mRNA and protein expression was observed for three days after single treatment with EGFR antisense morpholino oligomer. Furthermore, the growth of NCI-H125 cell line was significantly inhibited with treatment by EGFR antisense morpholino oligomer. Our results indicate that EGFR antisense morpholino oligomer represses the EGFR expression at both mRNA and protein level and inhibits the proliferation of NSCLC cell line suggesting that it may be a promising strategy as one of antisense therapies for NSCLC.
Insights
An antisense morpholino oligomer targeting the epidermal growth factor receptor (EGFR) effectively reduced EGFR expression and inhibited non-small cell lung cancer (NSCLC) cell proliferation. This suggests a promising new antisense therapy strategy for NSCLC.
Area of Science:
- Molecular Biology
- Cancer Research
- Oligonucleotide Therapeutics
Background:
- Epidermal growth factor receptor (EGFR) overexpression is common in various cancers, including lung cancer.
- Morpholino oligonucleotides offer stability and low toxicity for antisense applications.
Purpose of the Study:
- To investigate the efficacy of an EGFR antisense morpholino oligomer in a non-small cell lung cancer (NSCLC) cell line.
- To evaluate the impact on EGFR mRNA, protein expression, and cell proliferation.
Main Methods:
- Designed an EGFR antisense morpholino oligomer targeting the EGFR mRNA translation start site.
- Utilized a four base-mismatch morpholino oligomer as a control.
- Introduced oligomers into EGFR-overexpressing NCI-H125 NSCLC cells.
- Quantified EGFR mRNA via real-time RT-PCR and protein via ELISA.
Main Results:
- A single treatment with the EGFR antisense morpholino oligomer significantly repressed EGFR mRNA and protein expression for three days.
- Cell proliferation of the NCI-H125 cell line was significantly inhibited by the EGFR antisense morpholino oligomer treatment.
Conclusions:
- EGFR antisense morpholino oligomer effectively suppresses EGFR expression at both mRNA and protein levels.
- This oligomer demonstrates potential as a therapeutic strategy for NSCLC by inhibiting cancer cell proliferation.
