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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 Sep;85(9):966–971. doi: 10.1111/j.1349-7006.1994.tb02976.x

Synergistic Enhancement of Cisplatin Cytotoxicity by SN‐38, an Active Metabolite of CPT‐11, for Cisplatin‐resistant HeLa Cells

Yukihisa Minagawa 1, Junzo Kigawa 1, Hiroshi Ishihara 1, Hiroaki Itamochi 1, Naoki Terakawa 1,✉
PMCID: PMC5919584  PMID: 7961127

Abstract

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.

Keywords: CDDP, resistance, CPT‐11, HeLa cell

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