PMID- 10213503 OWN - NLM STAT- MEDLINE DCOM- 19990607 LR - 20220408 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 59 IP - 8 DP - 1999 Apr 15 TI - Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. PG - 1935-40 AB - We examined effects of the anti-epidermal growth factor receptor monoclonal antibody C225 on proliferation, cell cycle phase distribution, apoptosis, and radiosensitivity in squamous cell carcinoma (SCC) cell lines derived from head and neck cancer patients. Exposure to C225 in culture inhibits SCC proliferation in a time-dependent manner, and the degree of growth inhibition, compared to controls, ranges from 20 to 75%. Flow cytometry analysis demonstrates that C225 treatment induces accumulation of cells in G1, which is accompanied by a 2-3-fold decrease in the percentage of cells in S phase. C225 exposure also induces apoptosis in SCC populations, as demonstrated by flow cytometry analysis using dual stainings of merocyanine 540 and Hoechst 33342. Western blot analysis indicates that C225 exposure induces accumulation of hypophosphorylated retinoblastoma protein and increases expression of p27KIP1. An increase in Bax expression and concurrent decrease in Bcl-2 expression are observed when SCC cells are exposed to C225. Examination of C225 effects on radiation response in SCCs demonstrates enhancement in radiosensitivity and amplification of radiation-induced apoptosis. These effects are observed in both single-dose and fractionated radiation experiments. C225 represents a promising growth-inhibitory agent that can influence cellular proliferation, apoptosis, and radiosensitivity in SCCs of the head and neck. FAU - Huang, S M AU - Huang SM AD - Department of Human Oncology, University of Wisconsin School of Medicine and Comprehensive Cancer Center, Madison 53792-0600, USA. FAU - Bock, J M AU - Bock JM FAU - Harari, P M AU - Harari PM LA - eng GR - CA 66786/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - EC 2.7.10.1 (ErbB Receptors) RN - PQX0D8J21J (Cetuximab) SB - IM MH - Antibodies, Monoclonal/*pharmacology MH - Antibodies, Monoclonal, Humanized MH - *Apoptosis MH - Carcinoma, Squamous Cell/*immunology/pathology MH - Cell Division/drug effects MH - Cell Survival/drug effects/radiation effects MH - Cetuximab MH - ErbB Receptors/*immunology MH - G1 Phase/drug effects MH - Head and Neck Neoplasms/*immunology/pathology MH - Humans MH - Radiation Tolerance/*drug effects MH - Resting Phase, Cell Cycle/drug effects MH - Tumor Cells, Cultured EDAT- 1999/04/23 00:00 MHDA- 1999/04/23 00:01 CRDT- 1999/04/23 00:00 PHST- 1999/04/23 00:00 [pubmed] PHST- 1999/04/23 00:01 [medline] PHST- 1999/04/23 00:00 [entrez] PST - ppublish SO - Cancer Res. 1999 Apr 15;59(8):1935-40.