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.
