Title: 5-FU-induced apoptosis correlates with efficacy against human gastric and colon cancer xenografts in nude mice.
Abstract: Apoptosis may be an important mechanism by which cancer cells are killed by certain agents. It is reported here that apoptosis is a key event in the killing of human tumor cells by 5-fluorouracil (5-FU) in vivo. Apoptosis induced by 5-FU was determined using two human gastrointestinal tumor xenografts serially transplanted into nude mice: a gastric carcinoma (SC-1-NU) highly sensitive to 5-FU and a colon carcinoma (Co-4) less sensitive to 5-FU. Apoptosis was assayed using the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling method in paraffin-embedded tissue sections, and by flow-cytometric analysis. Apoptosis-positive cells increased gradually during treatment. 24 hours after the initiation of 5-FU treatment a maximum, of 15.4% of the Co-4 cells were apoptotic. 48 hours after the initiation of 5-FU treatment, apoptosis was found in 34% of the tumor cells in the SC-1-NU strain. Flow-cytometry demonstrated the increase of S-phase fractions in both strains after the administration of 5-FU, and this coincided with the appearance of apoptotic-positive cells. Although the intrinsic. TS activities of two strains differed, TS activities were markedly suppressed in both strains immediately after the administration of 5-FU. Concentration of 5-FU in RNA (F-RNA) increased gradually in both strains, reaching a maximum 24 hours after the administration of 5-FU. These results suggest that apoptosis and inhibition of DNA synthesis induced by 5-FU are closely associated with its antitumor effect.
Publication Year: 1997
Publication Date: 1997-05-01
Language: en
Type: article
Indexed In: ['pubmed']
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Cited By Count: 32
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