Prestimulation of head and neck cancer cells with growth factors enhances treatment efficacy
Hambek, M.; Werner, C.; Baghi, M.; Gstöttner, W.; Knecht, R.
Anticancer Research 26(2a): 1091-1095
2006
ISSN/ISBN: 0250-7005 PMID: 16619511 Document Number: 603225
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, A43.1, 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 cytotxic 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 lip 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.