The combination of ionizing radiation and expression of a wild type p53 gene via recombinant adenovirus induced a prominent tumour suppressing effect in human oral squamous cell carcinoma.
Human oral squamous cell carcinoma (SCC) cell lines HSC4 and SAS were infected with wild type p53 (wt-p53)-encoding adenovirus (AxCAip53) and subsequently irradiated to investigate the effectiveness of p53 gene therapy in combination with radiation therapy for treating oral SCC. Western blot analysis using anti-p53 monoclonal antibody showed that a large amount of mutant p53 protein was accumulated in HSC4 cells, while no detectable p53 protein was observed in SAS cells. The induction of p53 expression by AxCAip53 infection was clearly observed in both HSC4 and SAS cells. A clonogenic cell survival assay demonstrated that AxCAip53 infection alone, or X-irradiation alone, significantly inhibited the growth of cancer cells, but that combined treatment was most effective, even in mutant p53-accumulated HSC4 cells. Flow cytometric analysis showed that the apoptotic pathway was induced in virus treated and radiation treated cells. Taken together, these findings suggest that the combination of p53 gene therapy and radiation therapy has a possibility to effectively treat oral SCC defective in p53 function.
Wakasa
T
T
Department of Oral and Maxillofacial Radiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama City, Okayama 700-8525, Japan.
Inoue
T
T
Kawai
N
N
Murakami
J
J
Kishi
K
K
Fukui
K
K
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy / Q000628:therapy*; D002470:Cell Survival; D003131:Combined Modality Therapy; D005434:Flow Cytometry; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D009062:Mouth Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D014162:Transfection; D014407:Tumor Cells, Cultured