Induction of apoptosis in maxillary sinus cancer cells by 5-fluorouracil, vitamin A and radiation (FAR) therapy.
The triple combination of 5-fluorouracil (5-FU), vitamin A and radiation (FAR therapy) has been used since 1972 to treat malignant tumors of the head and neck at Kyushu University. Using nick end labeling of tumor specimens, cells of human maxillary sinus carcinomas were observed previously to undergo apoptosis in response to FAR therapy. The present study evaluated the in vitro effects of FAR therapy on a human maxillary sinus cancer (IMC-4) cell line. We further compared the effects of FAR therapy on this cell line with those effects seen on tissue samples taken from patients with maxillary sinus cancers. DNA electrophoresis and electron microscopic examination of the IMC-4 cells after treatment with FAR therapy revealed typical apoptotic features. The effects of 50-100 micrograms/ml 5-FU, 10(-4) M all-trans-retinoic acid and radiation to 6 Gy on IMC-4 cells were evaluated by trypan blue dye exclusion and a cell colony formation assay. 5-FU and radiation caused direct cell death, while vitamin A mainly inhibited cell growth. The combination of these treatment as FAR therapy synergistically enhanced cell death and inhibited cell growth. Flow cytometry demonstrated that FAR-treated cells were arrested in the G1 phase of the cell cycle before undergoing apoptosis. To further investigate possible biological parameters influencing a tumor's apoptotic sensitivity, we also examined the expression of p53 in human maxillary sinus cancer cells and analyzed the relationship between p53 expression and apoptosis. However, no relationship was found between these two markers at the time point studied.
Nakashima
T
T
Department of Otorhinolaryngology, Fukuoka City, Japan.
Masuda
M
M
Matsui
K
K
Inokuchi
A
A
Kuraoka
A
A
Komiyama
S
S
D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D003131:Combined Modality Therapy; D053938:DNA Fragmentation / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D008441:Maxillary Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D008443:Maxillary Sinus / Q000473:pathology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014801:Vitamin A / Q000008:administration & dosage
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D014801:Vitamin A; D005472:Fluorouracil