OBJECTIVES: In recent years, new chemotherapy regimens with promising activity, especially in first-line therapy (induction chemotherapy) of head and neck cancer (SCCHN), have been developed. Nevertheless, a major problem concerning the response of SCCHN to chemotherapy is the high percentage of resting cells (G0-phase cells) being resistant to chemotherapy. To overcome this phenomenon, the capacity of several cytokines to switch on cells into the division cycle and progress to the chemosensitive phases (S-, M-phases) was investigated. MATERIALS AND METHODS: Interleukin-6, serotonin, granulocyte colony stimulating factor (G-CSF) and epidermal growth factor (EGF) were used to stimulate G0-phase squamous cell cancer cells (Detroit 562, A431, UM-SCC 10B) for re-entry into the cell cycle to enhance the response to cisplatin. The proportion of G0-phase cells was detected through multicolor FACS analysis and Ki-67 staining. RESULTS: Cell cycle re-entry was most effective after combination treatment with serotonin + EGF. The proportion of G0-phase cells was significantly reduced after stimulation with serotonin + EGF (p <0.05). Corresponding to cell cycle re-entry, the cytotoxic effect of cisplatin was significantly (p <0.04) enhanced in the prestimulated compared to the control cells (cisplatin mono-treatment). CONCLUSION: Our investigations demonstrated for the first time that sensitizing G0-phase squamous cell carcinoma cells for chemotherapy is possible by prestimulation with target cytokines. Considering that up to 95% of tumor cells are in the resting (G0) phase of the cell cycle at the initiation of chemotherapy, prestimulation with EGF and serotonin could contribute to a synchronization of cancer cells. This would clearly enhance the cytotoxic effect.
