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Published on: March 30, 2019
Targeting cyclin D1 in non-small cell lung cancer and mesothelioma cells by antisense oligonucleotides
Shamsher S Saini1, Mark A Klein
1VA Medical Center, Section of Hematology/Oncology, Primary Care Service Line, Minneapolis, MN 55417, USA.
Background:
Cyclin D1 overexpression exists in multiple types of cancer and is a potential chemopreventive or therapeutic target.
Materials And Methods:
Non-small cell lung cancer and mesothelioma cells were incubated with antisense oligonucleotides (ASO) to cyclin D1 (CD1) and evaluated for effects on cellular proliferation, apoptosis, expression of cell cycle-specific proteins, and protein phosphorylation states.
Results:
ASO to CD1 inhibited proliferation of non-small lung cancer cells and mesothelioma cells. ASO induced apoptosis as determined by TUNEL assay. Western blot analysis of cell lysate showed that ASO inhibited the de novo synthesis of CD1, CD3, and CDK2 in multiple cell lines. Immunoprecipitation and immunoblotting with phosphoantibodies demonstrated that CD1, CD3, and CDK2 exist in a phosphorylated state.
Conclusion:
The work demonstrates that non-small cell lung cancer and mesothelioma cells respond to ASO-mediated cellular growth inhibition. These findings make ASO to CD1 attractive as a potential therapeutic for mesothelioma and non-small cell lung cancer.
Insights
Antisense oligonucleotides (ASO) targeting cyclin D1 (CD1) effectively inhibited growth and induced apoptosis in non-small cell lung cancer and mesothelioma cells, showing therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Cyclin D1 (CD1) is overexpressed in various cancers.
- CD1 is a potential target for cancer chemoprevention and therapy.
Purpose of the Study:
- To evaluate the efficacy of antisense oligonucleotides (ASO) targeting CD1 in non-small cell lung cancer (NSCLC) and mesothelioma.
- To assess the impact of CD1 ASO on cellular proliferation, apoptosis, and cell cycle protein expression.
Main Methods:
- Incubation of NSCLC and mesothelioma cells with ASO targeting CD1.
- Assessment of cellular proliferation and apoptosis (TUNEL assay).
- Western blot and immunoprecipitation to analyze protein expression and phosphorylation.
Main Results:
- ASO to CD1 significantly inhibited proliferation in both NSCLC and mesothelioma cells.
- ASO treatment induced apoptosis.
- ASO reduced the synthesis of CD1, CD3, and CDK2, and affected their phosphorylation states.
Conclusions:
- NSCLC and mesothelioma cells are responsive to ASO-mediated growth inhibition.
- ASO targeting CD1 represents a promising therapeutic strategy for NSCLC and mesothelioma.
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