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

作者: Ikuro Kimura , Hiroshi Ueoka , Nagio Takigawa , Taisuke Ohnoshi , Katsuyuki Kiura

DOI: 10.18926/AMO/32669

关键词: Molecular biologyVincaTeniposideCisplatinTopoisomeraseEtoposidePharmacologyBleomycinP-glycoproteinCell cultureBiology

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

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