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Tracking of STAT3 signaling for anticancer drug-discovery based on localized surface plasmon resonance
Sojin Song1, Anh H Nguyen, Jong Uk Lee
1Department of Chemical and Biological Engineering, Korea University, Seoul 136-713, South Korea. simsj@korea.ac.kr.
Abstract:
Signal transducer and activator of transcription 3 (STAT3) protein signaling is crucial for the survival, invasion, and growth of human cancer cells; thus, STAT3 protein is an ideal target for a new drug screening system. Herein, we developed a label-free sensor for anticancer drug-discovery based on the localized surface plasmon resonance (LSPR) shift response by tracking of STAT3 signaling including phosphorylation and dimerization. This enables ultrasensitive monitoring of the molecular interactions that occur on the surface of single gold nanoparticles. The red shift of the LSPR λmax was observed as 3.46 nm and 9.00 nm, respectively, indicating phosphorylation and dimerization of the STAT3 signaling pathway. In screening of anticancer candidates, the system worked well in the presence of STA-21 which inhibits STAT3 dimerization. The LSPR λmax shift in the inhibition condition is three times lower than that in the absence of an inhibitor. Interestingly, the system reveals high specificity, reproducibility and compatibility with real samples (MCF-7 cell line). Therefore, these results demonstrated that this system has strong potential to be an accurate and effective sensor for tracking of signaling pathways and drug screening of anticancer candidates for anticancer therapy.
Insights
We developed a label-free sensor to track Signal transducer and activator of transcription 3 (STAT3) protein signaling for anticancer drug discovery. This ultrasensitive system monitors STAT3 phosphorylation and dimerization, aiding in identifying effective cancer therapies.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Signal transducer and activator of transcription 3 (STAT3) protein signaling is vital for cancer cell survival, invasion, and growth.
- STAT3 protein represents an ideal target for novel anticancer drug discovery and development.
- Existing drug screening methods may lack the sensitivity or specificity required for complex signaling pathway analysis.
Purpose of the Study:
- To develop a label-free sensor system for the ultrasensitive monitoring of STAT3 signaling pathways.
- To enable real-time tracking of STAT3 phosphorylation and dimerization for anticancer drug screening.
- To demonstrate the potential of localized surface plasmon resonance (LSPR) for label-free biosensing in drug discovery.
Main Methods:
- Development of a label-free sensor utilizing localized surface plasmon resonance (LSPR) on gold nanoparticles.
- Monitoring of STAT3 protein phosphorylation and dimerization through LSPR wavelength shifts (λmax).
- Validation of the sensor system using STA-21, a known STAT3 dimerization inhibitor, and MCF-7 cancer cell lines.
Main Results:
- The LSPR sensor detected STAT3 phosphorylation and dimerization with distinct red shifts of 3.46 nm and 9.00 nm, respectively.
- The sensor demonstrated a three-fold reduction in LSPR shift in the presence of the STAT3 inhibitor STA-21, confirming specificity.
- The system exhibited high specificity, reproducibility, and compatibility with real biological samples, such as the MCF-7 cell line.
Conclusions:
- The developed label-free LSPR sensor system is effective for tracking STAT3 signaling pathways.
- This sensor shows significant potential as an accurate and sensitive tool for anticancer drug screening.
- The system offers a promising platform for advancing anticancer therapy development through precise molecular interaction monitoring.
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