Multidrug sensitivity phenotype of human lung cancer cells associated with topoisomerase II expression.

作者: Giuseppe Giaccone , Franco Zunino , Giovanni Capranico , Hans Beck , Adi F. Gazdar

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摘要: Patterns of drug sensitivities in relation to topoisomerase II gene expression and activity were studied eight human lung cancer cell lines not selected vitro for resistance. The cytotoxicities doxorubicin, etoposide, teniposide, cisplatin, camptothecin, 5-fluorouracil measured and, remarkably, these unselected shown have a common pattern multidrug sensitivity, i.e., sensitivity phenotype. In fact, significantly correlated with each other the lines, correlation being best II-targeted agents less strong weak 5-fluorouracil. Almost 1-log range difference was found this explained by cell-doubling time or cycle distribution. level positively highly epipodophyllotoxins, cisplatin seven lines. Although weaker, an association also observed between camptothecin cytotoxicity, while no However, non-small line neuroendocrine properties had very low levels gene, despite sensitive all drugs tested. I be cytotoxicity any A specific enzymatic assay teniposide-stimulated DNA cleavage showed that extent active present nuclear extracts paralleled expression. Furthermore, addition normal transcript, abnormally sized message rearrangement detected poorly small line. Therefore, expression, possibly mutations, may predict reduced several drugs, including cellular target than II. It is hypothesized might involved pathway death induced tumor which

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