MCF-7 growth inhibition by ultraviolet radiation and 5-fluorouracil: the importance of treatment sequence.
Effective treatment of certain cancers with 5-fluorouracil (5-FU) and irradiation is well established; however, the most effective combination of these agents remains controversial. Although 5-FU has been identified as a radiosensitizer, the mechanism of action remains unknown. To assess the effect of combination, 5-FU and ultraviolet (UV), we constructed a new in vitro model with MCF-7 human breast cancer cells that measures growth inhibition and morphologic changes in nuclear argyrophilic nucleolar organizer regions (AgNORs). Cells were incubated in media containing 0, 50, 100 and 500 ng/ml 5-FU for 48 h, they were also exposed to UV irradiation of 90 J/m(2) at the beginning, middle, or end of the incubation period. The cells were incubated for an additional 48 h with 5-FU free media. A combined treatment with 5-FU and UV radiation demonstrated an additive inhibitory effect. The strongest growth inhibition was observed when UV exposure was at the beginning of the 5-FU treatment at 5-FU concentrations of 100 and 500 ng/ml. To elucidate the activity of 5-FU radiosensitization, we investigated the aggregation Pof AgNOR, which we previously established to reflect rRNA inhibition. A combined treatment with 5-FU and UV radiation accelerated the rate of AgNOR aggregation at 5-FU concentrations of 50 and 100 ng/ml. The timing of UV irradiation did not affect the rate of AgNOR aggregation. A combined treatment with 5-FU and UV radiation showed an additive inhibitory effect on MCF-7 cell growth that might be explained, in part, by rRNA inhibition.
Hamaoka
T
T
First Department of Surgery, Kobe University School of Medicine, Kusunoki-chou 7-5-1, Chuo-ku, Kobe, Japan. qze16435@nifty.ne.jp
Furuya
Y
Y
Yamamoto
K
K
Kuroda
Y
Y
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002467:Cell Nucleus / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D009697:Nucleolus Organizer Region / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014467:Ultraviolet Therapy
C110656:2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; D000964:Antimetabolites, Antineoplastic; D012335:RNA, Ribosomal; D013778:Tetrazolium Salts; D005472:Fluorouracil