CC BY-NC-ND 4.0 · Laryngorhinootologie 2019; 98(S 02): S264
DOI: 10.1055/s-0039-1686024
Poster
Oncology

Thapsigargin (TG) and Trifluoperazine (TFP) suppress tumor growth and metastasis of head and neck cancer in vitro und in vivo

M Linxweiler
1   Universitätsklinikum des Saarlandes; HNO-Klinik, Homburg/S.
,
C Körbel
2   Universität des Saarlandes; Institut für klinisch-experimentelle Chirurgie, Homburg/S.
,
F Bochen
1   Universitätsklinikum des Saarlandes; HNO-Klinik, Homburg/S.
,
MD Menger
2   Universität des Saarlandes; Institut für klinisch-experimentelle Chirurgie, Homburg/S.
,
R Zimmermann
3   Universität des Saarlandes; Institut für medizinische Biochemie und Molekularbiologie, Homburg/S.
,
M Greiner
3   Universität des Saarlandes; Institut für medizinische Biochemie und Molekularbiologie, Homburg/S.
,
B Schick
1   Universitätsklinikum des Saarlandes; HNO-Klinik, Homburg/S.
› Author Affiliations
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Introduction:

Head and neck squamous cell carcinomas (HNSCCs) belong to the six most common cancers worldwide. In advanced tumor stages, therapeutic strategies are limited. As shown by our group, the majority of HNSCCs shows an overexpression of the SEC62 gene, which stimulates tumor metsatasis und induced tumor resistance against cellular stress. The SERCA inhibitor thapsigargin (TG) and the calmodulin antaonist trifluperazine (TFP) can functionally antagonize these effects oft he SEC62 gene poiting towards a possible therapeutic benefit of these substances in HNSCC patients.

Methods:

We investigated the effect of a TFP and TG treatment on cultured HNSCC cells witha focus on cell proliferation and migration in vitro. Additionally, the suppression of tumor growth and metastasis was evaluated in different murine xenograft models.

Results:

The treatment of HNSCC cells with TG as well as TFP induced dose dependent inhibition of tumor cell proliferation and migration in vitro. In the murine xenograft models, both substances were well tolerated and suppresses subcutaneous tumor growth in nude mice. First experiments in lymphogenic and hematogenic metastasis models showed a reduced size and number of metastases in animals treated with a combination of both substances.

Conclusion:

TFP and TG showed an inhibition of HNSCC tumor cell proliferation and metastasis in vitro and in vitro and therefore represent promising therapeutics in HNSCC patients.



Publication History

Publication Date:
23 April 2019 (online)

© 2019. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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