Transplatin, a cisplatin trans-isomer, may enhance the anticancer effect of 5-fluorouracil.
Transplatin (TDDP), a trans-isomer of cisplatin (CDDP), is well known to have faint cytotoxicity because its geometric structure allows less adduct formation with DNA than does CDDP. However, TDDP might have the potential to enhance the anticancer effect of 5-fluorouracil (5-FU) as well as CDDP. In this study, five gastric cancer cell lines were used. Cells were treated with 5-FU, TDDP, TDDP+5-FU, CDDP, and CDDP+5-FU, for 72 hrs. Synergistic effects between TDDP and 5-FU were observed in OCUM-2MD3, OCUM-2M, and OCUM-11, though they were not observed in MKN-45 or MKN-28. The cell lines in which synergistic effects were observed between TDDP and 5-FU were the same ones in which synergistic effects are shown between CDDP and 5-FU. The cell lines without synergism between 5-FU +TDDP/CDDP had lower thymidylate synthase (TS) activities than those with synergism, suggesting TS might be attributable to the synergistic mechanism. TDDP alone, compared to CDDP alone, gave rather low cytotoxicity for these cell lines. In conclusion, TDDP might be a clinically useful modulator of 5-FU.
Nakata
B
B
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. bunzo@med.osaka-cu.ac.jp
Yamagata
S
S
Kanehara
I
I
Shirasaka
T
T
Hirakawa
K
K
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D013237:Stereoisomerism; D013274:Stomach Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; C034697:transplatin; D002945:Cisplatin; D005472:Fluorouracil