Non-cross resistance of ZD0473 in acquired cisplatin-resistant lung cancer cell lines

Yoshiko Kawamura-Akiyama, Hitoshi Kusaba, Fumihiko Kanzawa, Tomohide Tamura, Nagahiro Saijo, Kazuto Nishio

研究成果: Contribution to journalArticle査読

22 被引用数 (Scopus)

抄録

ZD0473 is a new generation platinum agent that, in preclinical studies, shows evidence of an extended spectrum of anti-tumor activity and overcomes platinum resistance mechanisms. The drug contains a bulky methylpyridine ligand at its platinum center, which is responsible for its ability to overcome platinum resistance. We examined the growth inhibitory effects of ZD0473 in human lung cancer cell lines resistant to cisplatin in vitro. Four cisplatin resistant human lung cancer cell lines (PC-14/CDDP, SBC-3/CDDP, PC-9/CDDP, H69/CDDP) showed the expected resistance to cisplatin but were non-cross, or much less, resistant to ZD0473, as determined by an MTT assay. A reduction in the intracellular accumulation of cisplatin, but not of ZD0473, was observed in the PC-14/CDDP cells compared with the levels in PC-14 parental cells. The reduction in cisplatin accumulation is considered a major mechanism of the acquired cisplatin resistance in PC-14/CDDP cells. Therefore, the increase in platinum accumulation is considered a possible mechanism underlying the activity of ZD0473 in cisplatin-resistant cells. Glutathione-mediated resistance to cisplatin was also overcome by ZD0473 in PC-14/CDDP cells. In addition, we showed that the intraperitoneal administration of ZD0473 at its maximum tolerable dose in mice produced a marked in vivo antitumor activity against cisplatin-resistant PC-14/CDDP tumors. These results suggest that ZD0473 may be a potent agent in human lung cancer cells with multifactorial cisplatin resistance.

本文言語英語
ページ(範囲)43-50
ページ数8
ジャーナルLung Cancer
38
1
DOI
出版ステータス出版済み - 10 1 2002
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 呼吸器内科
  • 癌研究

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