Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung cancer cell line

Masakazu Chikamori, Nagio Takigawa, Katsuyuki Kiura, Masahiro Tabata, Takuo Shibayama, Yoshihiko Segawa, Hiroshi Ueoka, Taisuke Ohnoshi, Mitsune Tanimoto

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12 Citations (Scopus)

Abstract

Irinotecan is one of the most active drugs used in the treatment of small cell lung cancer (SCLC). 7-Ethyl-10-hydroxy-camptothecin (SN-38) is an active metabolite of irinotecan. We established an SN-38-resistant subline (SBC-3/SN-38) by continuous exposure of SN-38 to a human SCLC cell line, SBC-3. Using the 3-[4, 5-dimethyl-thiazol-2-yl] 2, 5-diphenyltetrazolium bromide assay, we evaluated the cytotoxicity of 17 anticancer agents. The SBC-3/SN-38 cells were 73-fold more resistant than the parental SBC-3 cells to SN-38 and showed cross-resistance not only to topoisomerase (topo) I inhibitors (irinotecan and topotecan), but also to topo II inhibitors (adriamycin and etoposide), antimicrotubule agents (vincristine, vindesine, vinorelbine and docetaxel), alkylating agents (cyclophosphamide and ifosfamide), platinum (cisplatin and carboplatin) and antifolate (methotrexate). Interestingly, the resistant subline reserved the sensitivity to bleomycin and 5-fluorouracil. The SBC-3/SN-38 cells had decreased topo I and II activity compared to the parent cells. The SN-38-resistant cell line, SBC-3/SN-38, will be useful to elucidate the mechanism of action of the topo I inhibitors.

Original languageEnglish
Pages (from-to)3911-3916
Number of pages6
JournalAnticancer research
Volume24
Issue number6
Publication statusPublished - Nov 2004

Keywords

  • Drug resistance
  • Irinotecan
  • Small cell lung cancer
  • Topoisomerase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Chikamori, M., Takigawa, N., Kiura, K., Tabata, M., Shibayama, T., Segawa, Y., Ueoka, H., Ohnoshi, T., & Tanimoto, M. (2004). Establishment of a 7-ethyl-10-hydroxy-camptothecin-resistant small cell lung cancer cell line. Anticancer research, 24(6), 3911-3916.