Induction of apoptosis in maxillary sinus cancer cells by 5-fluorouracil, vitamin A and radiation (FAR) therapy

Torahiko Nakashima, M. Masuda, K. Matsui, A. Inokuchi, A. Kuraoka, S. Komiyama

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Abstract

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 μg/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.

Original languageEnglish
JournalEuropean Archives of Oto-Rhino-Laryngology
Volume256
Issue numberSUPPL. 1
DOIs
Publication statusPublished - May 10 1999

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Maxillary Sinus Neoplasms
Vitamin A
Fluorouracil
Radiotherapy
Apoptosis
Radiation
Cell Death
Cell Line
Neoplasms
Trypan Blue
Maxillary Sinus
G1 Phase
Growth
Tretinoin
Electrophoresis

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology

Cite this

Induction of apoptosis in maxillary sinus cancer cells by 5-fluorouracil, vitamin A and radiation (FAR) therapy. / Nakashima, Torahiko; Masuda, M.; Matsui, K.; Inokuchi, A.; Kuraoka, A.; Komiyama, S.

In: European Archives of Oto-Rhino-Laryngology, Vol. 256, No. SUPPL. 1, 10.05.1999.

Research output: Contribution to journalArticle

Nakashima, Torahiko ; Masuda, M. ; Matsui, K. ; Inokuchi, A. ; Kuraoka, A. ; Komiyama, S. / Induction of apoptosis in maxillary sinus cancer cells by 5-fluorouracil, vitamin A and radiation (FAR) therapy. In: European Archives of Oto-Rhino-Laryngology. 1999 ; Vol. 256, No. SUPPL. 1.
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