Enhancement of docetaxel efficacy in head and neck cancer treatment by G0 cell stimulation.
OBJECTIVE
Docetaxel has recently taken part in new chemotherapy regimens with promising activity especially in the first line therapy (induction chemotherapy) of head and neck cancer (SCCHN). 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 we have investigated the capacity of several cytokines to switch on cells into division cycle and progress to the chemosensitive phases (S, M-phase).


METHODS
Il-6, Serotonin, G-CSF and EGF were used to stimulate G0-phase squamous cell cancer cells (Detroit 562, A431, UM-SCC 10B) for reentry in the cell cycle to enhance the response to docetaxel. The proportion of G0-phase cells was detected through multicolor FACS analysis and Ki67 staining.


RESULTS
Cell cycle reentering 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 reentry the cytotoxic effect of docetaxel was significantly (p<0.04) enhanced in the prestimulated cells compared to the control (docetaxel monotreatment).


CONCLUSIONS
Our investigations demonstrate for the first time that sensitizing G0 phase squamous cell carcinoma cells for docetaxel treatment 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.
Hambek
Markus
M
ENT-Center, University Clinic Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt / Main, Germany. knecht@em.uni-frankfurt.de
Werner
Christian
C
Baghi
Mehran
M
Gstöttner
Wolfgang
W
Knecht
Rainald
R
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000077143:Docetaxel; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D015850:Interleukin-6 / Q000627:therapeutic use; D019394:Ki-67 Antigen / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D012701:Serotonin / Q000627:therapeutic use; D043823:Taxoids / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015850:Interleukin-6; D019394:Ki-67 Antigen; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D012701:Serotonin