PUBLICATION

PCR-based zebrafish model for personalised medicine in head and neck cancer

Authors
Al-Samadi, A., Tuomainen, K., Kivimäki, A., Salem, A., Al-Kubati, S., Hyytiäinen, A., Parikka, M., Mesimäki, K., Wilkman, T., Mäkitie, A., Grenman, R., Salo, T.
ID
ZDB-PUB-190724-31
Date
2019
Source
Journal of translational medicine   17: 235 (Journal)
Registered Authors
Keywords
Chemotherapy, Drug screening, In vivo, Model, Oral cancer, Xenograft
MeSH Terms
  • Animals
  • Carcinoma, Squamous Cell/genetics
  • Carcinoma, Squamous Cell/pathology
  • Carcinoma, Squamous Cell/therapy
  • Cell Line, Tumor
  • Cisplatin/therapeutic use
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Head and Neck Neoplasms/drug therapy
  • Head and Neck Neoplasms/genetics*
  • Head and Neck Neoplasms/therapy*
  • Humans
  • Larva
  • Polymerase Chain Reaction*
  • Precision Medicine*
  • Xenograft Model Antitumor Assays
  • Zebrafish
PubMed
31331338 Full text @ J Transl Med
Abstract
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.
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.
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.
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.
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