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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalLung Cancer
Volume38
Issue number1
DOIs
Publication statusPublished - Oct 1 2002
Externally publishedYes

Fingerprint

Cisplatin
Lung Neoplasms
Cell Line
Platinum
amminedichloro(2-methylpyridine)platinum(II)
Glutathione
Neoplasms
Ligands
Growth
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Non-cross resistance of ZD0473 in acquired cisplatin-resistant lung cancer cell lines. / Kawamura-Akiyama, Yoshiko; Kusaba, Hitoshi; Kanzawa, Fumihiko; Tamura, Tomohide; Saijo, Nagahiro; Nishio, Kazuto.

In: Lung Cancer, Vol. 38, No. 1, 01.10.2002, p. 43-50.

Research output: Contribution to journalArticle

Kawamura-Akiyama, Y, Kusaba, H, Kanzawa, F, Tamura, T, Saijo, N & Nishio, K 2002, 'Non-cross resistance of ZD0473 in acquired cisplatin-resistant lung cancer cell lines', Lung Cancer, vol. 38, no. 1, pp. 43-50. https://doi.org/10.1016/S0169-5002(02)00175-7
Kawamura-Akiyama, Yoshiko ; Kusaba, Hitoshi ; Kanzawa, Fumihiko ; Tamura, Tomohide ; Saijo, Nagahiro ; Nishio, Kazuto. / Non-cross resistance of ZD0473 in acquired cisplatin-resistant lung cancer cell lines. In: Lung Cancer. 2002 ; Vol. 38, No. 1. pp. 43-50.
@article{319fdf581b15408999e4cf7f3722c83a,
title = "Non-cross resistance of ZD0473 in acquired cisplatin-resistant lung cancer cell lines",
abstract = "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.",
author = "Yoshiko Kawamura-Akiyama and Hitoshi Kusaba and Fumihiko Kanzawa and Tomohide Tamura and Nagahiro Saijo and Kazuto Nishio",
year = "2002",
month = "10",
day = "1",
doi = "10.1016/S0169-5002(02)00175-7",
language = "English",
volume = "38",
pages = "43--50",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Non-cross resistance of ZD0473 in acquired cisplatin-resistant lung cancer cell lines

AU - Kawamura-Akiyama, Yoshiko

AU - Kusaba, Hitoshi

AU - Kanzawa, Fumihiko

AU - Tamura, Tomohide

AU - Saijo, Nagahiro

AU - Nishio, Kazuto

PY - 2002/10/1

Y1 - 2002/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0036806705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036806705&partnerID=8YFLogxK

U2 - 10.1016/S0169-5002(02)00175-7

DO - 10.1016/S0169-5002(02)00175-7

M3 - Article

C2 - 12367792

AN - SCOPUS:0036806705

VL - 38

SP - 43

EP - 50

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

IS - 1

ER -