Introduction. Besides surgery, radiotherapy, in combination with chemotherapy, is the major treatment option for head and neck squamous cell carcinomas (HNSCC). Next to the classical photon based irradiation, particle therapy is gaining more and more interest. Previous reports implicated AZD3965, an inhibitor of the monocarboxylate (lactate) transporter 1 (MCT1), as a promising radio-sensitizing drug for HNSCC. Here, we investigated the effects of carbon irradiation with and without AZD3965 on HPV^pos and HPV^neg HNSCC cell lines.

Material and methods. Three HPV^neg and three HPV^pos HNSCC cell lines were grown under standard conditions until reaching 80% confluence. 700,000 cells were added to each well of a six well plate the day before irradiation. 8 h after cell seeding, AZD3965 (1 µmol/L) or the same volume of DMSO (control) was added to the cell medium and incubation was continued for 24 more hours. Irradiation of cells was performed at the Marburg Ion-Beam Therapy Center with 4 Gy of carbon ions (C12). Non-irradiated control cells were carried along. Subsequently, cells were incubated for 24 h and prepared for cell cycle analysis.

Results. All cell lines responded with a cell cycle block to particle irradiation. The most pronounced effect was seen in HPV^pos HNSCC cell lines. Deploying AZD3965, HPV^neg HNSCC cells exhibited a significantly increased cell cycle block, whereas only a minor effect was seen in HPV^pos HNSCC cells.

Discussion. Inhibiting MCT1 using AZD3965 could radio-sensitize in particular HPV^neg HNSCC cell lines, which could be explained by previous observations, demonstrating a higher preference of HPV^neg HNSCC cells for ATP production via glycolysis compared to HPV^pos HNSCC cells.

This study was funded by the "Marburger Förderprogramm MIT-Forschung"

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