Open AccessSynergistic Enhancement of Cisplatin Cytotoxicity by SN‐38, an Active Metabolite of CPT‐11, for Cisplatin‐resistant HeLa Cells
Author(s) -
Minagawa Yukihisa,
Kigawa Junzo,
Ishihara Hiroshi,
Itamochi Hiroaki,
Terakawa Naoki
Publication year - 1994
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1994.tb02976.x
Subject(s) - hela , cisplatin , cytotoxicity , cell culture , metabolite , buthionine sulfoximine , glutathione , chemistry , intracellular , cancer cell , microbiology and biotechnology , cancer research , cell , biology , pharmacology , biochemistry , in vitro , chemotherapy , cancer , enzyme , genetics
A cisplatin ( cis ‐diamininedichloroplatinuin(II); CDDP)‐resistant HeLa cell line (HeLa/CDDP cells), which showed more than 8‐fold resistance to CDDF compared to the parent cells, was newly established for this study. HeLa/CDDP cells accumulated 50% less platinum than the parent cells. There was no difference in intracellular glutathione (GSH) content between the parent and HeLa/ CDDP cells. The dose modification factor by DL‐buthionine‐S, R‐sulfoximine (BSO) pretreatment was similar in both cell lines. HeLa/CDDP cells had cross‐resistance to diammine (l, l‐cyclobutanedicarboxylato)platinum(II) (CBDCA), ( cis ‐diammine (glycolato)platinum (254‐S), but not to (‐)‐(R)‐2‐aminomethylpyrrolidine(1,1‐cyclobutanedicarboxylato)platinum(II) (DWA2114R), adriamycin, or VP‐16. HeLa/CDDP cells showed a collateral sensitivity to 7‐ethyl‐10‐hydroxycampto‐thecin (SN‐38), an active metabolite of 7‐ethyl‐10‐[4‐(l‐piperidino)‐l‐piperidino]carbonyloxycamptothecin (CPT‐11). Furthermore, isobologram analysis indicated synergistic interaction of CDDP and SN‐38 only for HeLa/CDDP cells. The present study suggests that combination therapy with CDDP and CPT‐11 may he potentially useful in the treatment of some patients with CDDP‐resistant cancer.