Anti-HER2-antibody enhances irradiation-induced growth inhibition in head and neck carcinoma.
To explore the antiproliferative effects of rhumAbHER2 on head and neck squamous carcinoma cell (HNSCC) lines and breast cancer cell lines (BCCLs) and to evaluate the combined effects with irradiation, 2 human HNSCC lines and 2 BCCLs were exposed to rhumAbHER2 with or without irradiation. The results showed that combined treatment enhanced the growth and colonization inhibitory effects of rhumAbHER2 or irradiation. Interestingly, the apoptotic cell fraction produced by irradiation disappeared on combined treatment. This disappearance was associated with repression of p53 and Bax upregulation induced by irradiation, but conservation of the upregulation of p27. Based on these results, rhumAbHER2 and irradiation may be a new strategy for treating HNSCC and breast cancers. In addition, the upregulation of cyclin-dependent kinase inhibitors by rhumAbHER2 may occur upstream of irradiation-induced p53 upregulation.
Uno
M
M
Department of Radiation Oncology, Kawasaki Medical School, Okayama, Japan. unomako@med.kawasaki-m.ac.jp
Otsuki
T
T
Kurebayashi
J
J
Sakaguchi
H
H
Isozaki
Y
Y
Ueki
A
A
Yata
K
K
Fujii
T
T
Hiratsuka
J
J
Akisada
T
T
Harada
T
T
Imajo
Y
Y
D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000532:radiotherapy / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy / Q000628:therapy; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D018734:Genes, erbB-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D020287:In Situ Nick-End Labeling; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human