gms | German Medical Science

Introduction: Statins as Simvastatin (Sim) inhibit endogenous cholesterol synthesis, which is an essential component in cell membrane integrity and membrane-anchored proteins. We examined the effect of Sim in combination with Docetaxel (DTX) on tumor growth of head and neck squamous cell carcinoma (HNSCC) ex vivo.

Methods: For reference purposes the cell line KB was studied regarding cytostatic effects of Sim alone and in binary combination with DTX. The pharmacological effect was quantified using the MTT-test. Biopsies of 49 HNSCC were tested with DTX either alone or in combination with Sim in the FLAVINO-Assay. Epithelial cells were detected by Cy2-labeled anti-Cytokeratin-antibodies. Ex-vivo colony formation of epithelial cells (CF) was counted using immunofluorescent microscopy. Analysis of the mode of action was done according to the formula published by Jin (2004).

Results: Sim alone reduced MTT-turnover of KB in a dose-dependent manner as well as in combination with DTX. In the subgroup of 18/49 HNSCC allowing reliable analysis (≥4 cytokeratin-positive colonies in control cavities), Sim significantly suppressed CF in 18/18 HNSCC with IC50 in concentrations achievable in vivo. Calculation of the mode of action revealed primarily additivity of effects exerted by Sim and DTX (78%).

Conclusion: Our study highlights the suppressive effect of Sim on growth of HNSCC ex vivo. In combination with the guideline-conform chemotherapeutic DTX, Sim mainly acted additive. These findings suggest, that inclusion of Sim may be useful and able to support therapy of HNSCC in future treatment regimens. Still, more testing of Sim in combination with other possible pharmaceuticals regarding the combinatory effects on HNSCC ex vivo are needed.

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