Prestimulation of head and neck cancer cells with growth factors enhances treatment efficacy.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Hambek
Markus
M
ENT-Center, University Clinic Frankfurt, 60590 Frankfurt/Main, Germany.
Werner
Christian
C
Baghi
Mehran
M
Gstöttner
Wolfgang
W
Knecht
Rainald
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction
D000970:Antineoplastic Agents; D006133:Growth Substances; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016179:Granulocyte Colony-Stimulating Factor; D012701:Serotonin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D002945:Cisplatin