In vitro studies of 5-FU sensitivity on uterine cervical cancer cell lines--comparison between squamous cell carcinoma and adenocarcinoma

In order to improve the postoperative survival rate of patients with cervical cancer, we have treated them with adjuvant chemotherapy (oral Tegafur) and proved this treatment to be useful. However, the prognosis of cervical adenocarcinoma cases has not been improved yet. In this study, 5-FU sensitivity, morphological changes and DNA metabolism of cultured cervical cancer cells were examined using OMC-1 and OMC-4 cell line originating from cervical squamous cell carcinoma and adenocarcinoma, respectively. The EC 50 (Effective Concentration for 50% Cell Kill) of 5-FU on OMC-1 and OMC-4 cells after 96 hours of incubation with 5-FU was 0.13 micrograms/ml and 9.1 micrograms/ml, respectively. The morphological changes were more prominent in OMC-1 cells than in OMC-4 cells after 192 hours of incubation with 0.1 micrograms/ml of 5-FU. The incorporation of 3H-deoxyuridine into the DNA was inhibited more significantly in OMC-1 cells than in OMC-4 cells even at a low concentration of 5-FU. The intracellular FdUMP and thymidylate synthetase (TS) inhibition rate of OMC-1 and OMC-4 after 96 hours of incubation with 0.1 microgram/ml of 5-FU was 4.7 pmol/g and less than 2.6 pmol/g, 58.7% and 60.0%, respectively. These results suggest that 5-FU sensitivity of cervical adenocarcinoma cell line (OMC-4) is lower than that of cervical squamous carcinoma cell line (OMC-1) and it may owe much not to the TS inhibition rate but to the intracellular FdUMP.