Topoisomerase IIα content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell lines

Kohichi Yamazaki, Hiroshi Isobe, Tarou Hanada, Tomoko Betsuyaku, Atsushi Hasegawa, Nobuyuki Hizawa, Shigeaki Ogura, Yoshikazu Kawakami

研究成果: Article査読

18 被引用数 (Scopus)

抄録

Purpose: Topoisomerase IIα content, topoisomerase II catalytic activity and drug sensitivities to the topoisomerase II inhibitors, doxorubicin and etoposide, were examined in a panel of 14 unselected human lung cancer cell lines in order to determine the relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhibitors. Methods: Drug sensitivities were determined using a microculture tetrazolium assay. The topoisomerase IIα levels were determined by Western blot analysis and the topoisomerase II catalytic activity was determined using a decatenation assay of kinetoplast DNA, using nuclear protein from cells of each cell line. Results: Drug sensitivity tests revealed that small-cell lung cancer (SCLC) cell lines were more sensitive to drugs than non-small-cell lung cancer (NSCLC) cell lines. The relative topoisomerase IIα levels and relative topoisomerase II catalytic activity from SCLC cell lines (mean ± SD 0.89 ± 0.54 and 5.3 ± 3.4, respectively) were slightly higher than those from NSCLC cell lines (0.78 ± 0.56 and 4.0 ± 2.8, respectively), but the differences were not statistically significant, and not sufficient to account for the variation in drug sensitivities. Moreover, no clear association was observed between the topoisomerase IIα levels or the topoisomerase II catalytic activity and drug sensitivities in the cell lines studied. Conclusions: These findings suggest that the difference in drug sensitivities to doxorubicin and etoposide in human lung cancer cell lines might not be explainable by the topoisomerase IIα levels and topoisomerase II catalytic activity. Moreover, our results suggest that the topoisomerase IIα levels and topoisomerase II catalytic activity may play a minor role in the determination of clinical drug resistance of human lung cancers.

本文言語English
ページ(範囲)192-198
ページ数7
ジャーナルCancer Chemotherapy and Pharmacology
39
3
DOI
出版ステータスPublished - 1996 12

ASJC Scopus subject areas

  • 腫瘍学
  • 毒物学
  • 薬理学
  • 癌研究
  • 薬理学(医学)

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