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Int J Cancer. 2003 Sep 1;106(3):324-6.

Overexpression of thymidylate synthase mediates desensitization for 5-fluorouracil of tumor cells.

Author information

1
Department of Obstetrics and Gynecology, Jichi Medical School, Yakushiji, Minamikawachi, Tochigi 329-0498, Japan. saga@jichi.ac.jp

Abstract

The prognosis of cancers of various organs overexpressing thymidylate synthase (TS) has been reported to be poor. It has been suggested that the poor prognosis is partly due to a low sensitivity of TS-overexpressing tumors to TS-targeting 5-fluorouracil (5-FU). To investigate the relationship between TS expression and sensitivity to 5-FU, we used the TS-overexpressing cervical cancer cell line SKG-II/TS and SKG-I/TS that had been established by TS gene transfer. The 50% growth inhibitory concentration (IC(50)) of 5-FU for SKG-II/TS was 24 +/- 6.0 microM, which was 6 times as high as that for the control (4.0 +/- 1.1 microM), showing significantly decreased sensitivity to 5-FU (p < 0.01). The IC(50) of 5-FU for SKG-I/TS was 90 +/- 15 microM, which was over 2 times as high as that for the control (40 +/- 0.6 microM), showing significantly decreased sensitivity to 5-FU (p < 0.05). Thus, TS-overexpressing tumors have decreased sensitivity to 5-FU, which may be one of the factors that determine the prognosis of these tumors.

PMID:
12845668
DOI:
10.1002/ijc.11221
[Indexed for MEDLINE]
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