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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Research

Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib

Authors: Liwei Lang, Chloe Shay, Yuanping Xiong, Parth Thakkar, Ron Chemmalakuzhy, Xuli Wang, Yong Teng

Published in: Journal of Hematology & Oncology | Issue 1/2018

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Abstract

Background

Inhibition of metastasis of head and neck squamous cell carcinoma (HNSCC) is one of the most important challenges in cancer treatment. Src, a non-receptor tyrosine kinase, has been implicated as a key promoter in tumor progression and metastasis of HNSCC. However, Src therapy for HNSCC is limited by lack of efficient in vivo delivery and underlying mechanisms remain elusive.

Methods

Src knockdown cells were achieved by lentiviral-mediated interference. Cell migration and invasion were examined by wound healing and Transwell assays. Protein levels were determined by Western blot and/or immunohistochemistry. The Src inhibitor saracatinib was loaded into self-assembling nanoparticles by the solvent evaporation method. An experimental metastasis mouse model was generated to investigate the drug efficacy in metastasis.

Results

Blockade of Src kinase activity by saracatinib effectively suppressed invasion and metastasis of HNSCC. Mechanistic assessment of the drug effects in HNSCC cells showed that saracatinib induced suppression of Src-dependent invasion/metastasis through downregulating the expression levels of Vimentin and Snail proteins. In tests in mice, saracatinib loaded into the novel multifunctional nanoparticles exhibited superior effects on suppression of HNSCC metastasis compared with the free drug, which is mainly attributed to highly specific and efficient tumor-targeted drug delivery system.

Conclusions

These findings and advances are of great importance to the development of Src-targeted nanomedicine as a more effective therapy for metastatic HNSCC.
Appendix
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Metadata
Title
Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib
Authors
Liwei Lang
Chloe Shay
Yuanping Xiong
Parth Thakkar
Ron Chemmalakuzhy
Xuli Wang
Yong Teng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0623-3

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