Establishment and characterization of an etoposide-resistant human small cell lung cancer cell line.

N. Takigawa, T. Ohnoshi, H. Ueoka, Katsuyuki Kiura, I. Kimura

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Abstract

An etoposide-resistant subline, SBC-3/ETP, from a human small cell lung cancer cell line, SBC-3, was developed by continuous exposure to increasing concentrations of etoposide in culture. The SBC-3/ETP was 52.1-fold more resistant to etoposide than the parent cell line. The SBC-3/ETP was highly cross-resistant to teniposide, adriamycin, vinca alkaloids, 4-hydroperoxycyclophosphamide, CPT-11 and mitomycin C, and marginally cross-resistant to cisplatin, while the subline showed a collateral sensitivity to bleomycin. Topoisomerase I activity in the SBC-3/ETP was reduced to an extent of one half and topoisomerase II activity to an extent of one eighth in comparison with those of the SBC-3. Intracellular accumulation of [3H]-etoposide in the SBC-3/ETP was significantly lower in comparison to the SBC-3. An overexpression of MDR1 mRNA, and the presence of its product, P-glycoprotein, were detected in the SBC-3/ETP by Northern blotting and flowcytometry using a monoclonal antibody of the protein, MRK16. These results indicate that a decreased activity of topoisomerase II is the major factor for the development of etoposide resistance, and that an overexpression of the MDR1 gene is responsible, in part, for the development of resistance to the drug and some structurally unrelated compounds such as adriamycin and vinca alkaloids.

Original languageEnglish
Pages (from-to)203-212
Number of pages10
JournalActa Medica Okayama
Volume46
Issue number3
Publication statusPublished - Jun 1992

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Small Cell Lung Carcinoma
Etoposide
Cells
Cell Line
Vinca Alkaloids
Type II DNA Topoisomerase
irinotecan
perfosfamide
Doxorubicin
Teniposide
Type I DNA Topoisomerase
Bleomycin
P-Glycoprotein
Mitomycin
Drug Resistance
Northern Blotting
Cisplatin
Genes
Monoclonal Antibodies
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Establishment and characterization of an etoposide-resistant human small cell lung cancer cell line. / Takigawa, N.; Ohnoshi, T.; Ueoka, H.; Kiura, Katsuyuki; Kimura, I.

In: Acta Medica Okayama, Vol. 46, No. 3, 06.1992, p. 203-212.

Research output: Contribution to journalArticle

Takigawa, N, Ohnoshi, T, Ueoka, H, Kiura, K & Kimura, I 1992, 'Establishment and characterization of an etoposide-resistant human small cell lung cancer cell line.', Acta Medica Okayama, vol. 46, no. 3, pp. 203-212.
Takigawa, N. ; Ohnoshi, T. ; Ueoka, H. ; Kiura, Katsuyuki ; Kimura, I. / Establishment and characterization of an etoposide-resistant human small cell lung cancer cell line. In: Acta Medica Okayama. 1992 ; Vol. 46, No. 3. pp. 203-212.
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