gms | German Medical Science

Objective: Chemotherapy in head and neck cancer (HNSCC) is effective, yet associated with potentially severe systemic side effects. In this regard, the additional effect of hyperthermia has not yet been conclusively clarified up to now. Targeted drug delivery with nanoparticles carrying chemotherapeutic agents combined with local hyperthermia could improve treatment efficacy and reducing systemic side effects. This study investigates the impact of hyperthermia combined with various chemotherapeutics in vitro.

Materials: Fetal calf serum (FCS) superior. EMEM, DMEM: F-12 and McCoy’s 5A. Hydrocortisone. Water used in all experiments was of ultrapure quality produced by the Milli-Q^® system. FaDu (ATCC^® HTB-43™), SCC-9 (ATCC^® CRL-1629™), A-253 (ATCC^® HTB-41™) and Detroit 562 (ATCC^® CCL-138™) cell lines.

Methods: Four HNSCC cell lines (FaDu, SCC-9, A253. Detroit562) were exposed to temperatures of 42°C, 45°C and 47°C for one hour and to different doses of the chemotherapeutics Cisplatin, Docetaxel and Mitoxantron. The effects of these various treatment combinations were determined using live cell microscopy based on cell growth. Additionally, western blot analyses and immunocytochemistry stainings on relevant targets, such as heatshock proteins, were performed.

Results: Hyperthermia at 42°C did only show a small or even a negative effect on all cells. However, at 45°C, a significant decrease in cell growth was observed in all cell lines. At 47°C, the cell number decreased dramatically in all cell lines followed by a slow recovery of Detroit562 and FaDu after 48 hours. As hyperthermia alone at 45°C is effective already, synergistic effects of hyperthermia and chemotherapeutics can mostly be observed at 42°C and to some extent at 45°C. All chemotherapeutics applied at 47°C led to complete inhibition of cell growth. The levels of heat shock proteins varied with higher temperatures throughout the different cell lines but no direct correlation to cell survival was identified.

Conclusion: In this study, combinations of chemotherapeutics with hyperthermia of 45°C and 47°C were highly effective in exterminating HNSCC cell lines. In contrast, mild hyperthermia at 42°C with low doses of Docetaxel led to enhanced proliferation. These pioneering results indicate that, targeted drug delivery by magnetic nanoparticles and appropriate hyperthermia in the range of 45°C in the tumor site deserves further experimental evaluation as a potentially clinically effective treatment option for HNSCC.