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Published on: September 29, 2018
PCR-based zebrafish model for personalised medicine in head and neck cancer
Ahmed Al-Samadi1, Katja Tuomainen2, Anne Kivimäki2
1Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki 1, C223b (Haartmaninkatu 8), P.O. Box 63, 00014, Helsinki, Finland. ahmed.al-samadi@helsinki.fi.
Background:
Currently, in vivo model for personalised cancer drug testing is challenging. A zebrafish larvae xenograft model has been applied in recent years to cancer research, particularly for drug testing purposes, showing promising results in drug testing against patient-derived tumour xenografts. Currently, these xenograft models apply imaging techniques to measure drug efficacy. However, this method carries several limitations, including timely imaging, thereby reducing the available number of tested fish and drugs. Here, we propose a PCR-based fast assay to evaluate drug efficacy in a zebrafish larvae xenograft model.
Methods:
We tested two primary and corresponding metastatic head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived tongue cancer sample applying zebrafish larvae xenograft model. Cisplatin efficacy was tested using imaging technique and compared the results with PCR-based methods. Drug screening of eight compounds was applied on both cell lines and patient sample using PCR.
Results:
In a head-to-head comparison, all the three techniques (imaging, quantitative PCR, and droplet digital PCR) showed similar reduction of the cancer cells growth after cisplatin treatment. Using the quantitative PCR assay, we demonstrated a dose-dependent response of HNSCC cells to cisplatin. Drug screening results of four HNSCC cell lines and patient sample revealed different drug efficacy between tested cancer cells.
Conclusion:
We introduce a novel, easy, fast and cost-effective PCR-based in vivo zebrafish larvae assay to test the response of cell lines and clinical tumour samples to anti-cancer drugs. This method goes hand-by-hand with the commonly used imaging assay.
Insights
A new PCR-based assay offers a faster, cost-effective method for personalized cancer drug testing in zebrafish larvae xenografts. This approach accurately assesses drug efficacy in both cell lines and patient tumors, improving upon traditional imaging techniques.
Area of Science:
- Oncology
- Zebrafish Models
- Molecular Biology
Background:
- In vivo personalized cancer drug testing remains challenging.
- Zebrafish larvae xenografts show promise for drug testing against patient-derived tumors.
- Current imaging methods for drug efficacy assessment in xenografts have limitations, including time constraints.
Purpose of the Study:
- To develop a novel, rapid, and cost-effective PCR-based assay for evaluating anti-cancer drug efficacy.
- To compare the efficacy of the PCR-based assay with traditional imaging techniques in a zebrafish larvae xenograft model.
- To screen multiple compounds for anti-cancer activity using the developed assay.
Main Methods:
- Established a zebrafish larvae xenograft model using head and neck squamous cell carcinoma (HNSCC) cell lines and a patient-derived tumor sample.
- Evaluated cisplatin efficacy using both imaging and PCR-based methods (quantitative PCR and droplet digital PCR).
- Performed drug screening of eight compounds on HNSCC cell lines and patient samples via PCR.
Main Results:
- PCR-based methods (qPCR and ddPCR) demonstrated comparable results to imaging in assessing cisplatin's reduction of cancer cell growth.
- The quantitative PCR assay confirmed a dose-dependent response of HNSCC cells to cisplatin.
- Drug screening revealed varying efficacies of tested compounds across different HNSCC cell lines and the patient sample.
Conclusions:
- Introduced a novel, efficient, and economical PCR-based assay for in vivo drug response evaluation in zebrafish larvae.
- The assay is suitable for testing both cancer cell lines and clinical tumor samples.
- This PCR method complements existing imaging techniques for enhanced drug efficacy assessment.
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