Advertisement

Chinese Journal of Cancer Research

, Volume 9, Issue 3, pp 178–182 | Cite as

Resistant mechanisms of cisplatin in human lung adenocarcinoma cell line A549DDP

  • Zhan Maocheng 
  • Liu Xuyi 
  • Cai Peng 
  • Xu Guangwei 
Basic Investigations
  • 27 Downloads

Abstract

To study the resistant mechanisms of cisplatin in human lung adenocarcinoma cell line A549DDP. A549DDP cells was established by stepwise increasing concentration of cisplatin (CDDP) in medium. Interstrand cross-linked DNA (ICL) was measured by ethidium bromide fluorescence assay. The intracellular and intranuclear accumulation of cisplatin was measured by atomic absorption spectrometry. The removal of GS-X was determined by FCM and fluorescence microscopy. Results: The A549DDP cell line was 8.9-fold resistance relative to the parental A549 cell line. The formation of ICL in A549 was 6.28 times higher than that in A549DDP cells. The intracellular and intranuclear accumulation of cisplatin in A549 cells was 5.9 times and 4.1 times higher than that in A549DDP cells, respectively. The ability of GS-X pump pumped GS-X complex (GS-Pt) in A549DDP cells was higher than that in A549. The repair rate in A549DDP cells was 2 times higher than that in A549. Conclusions: Decreased accumulation and increased export of cisplatin might be the main mechanism of cisplatin resistant A549DDP cells while the enhanced repair capacity of DNA may play a role in CDDP resistance.

Key words

Resistance mechanism Human A549 Cisplatin Interstrand cross-link Accumulation DNA repair capacity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Loehrer PJ, Einhorn L. Cisplatin. Ann Intern Med 1984; 100:704.PubMedGoogle Scholar
  2. 2.
    Gilbert C. Cellular response to cisplatin. J Biol Chem 1994; 269:787.Google Scholar
  3. 3.
    Johnson SW, Shen DW, Pastan I, et al. Cross-resistance, cisplatin accumulation, and cisplatin-DNA adduct formation and removal in cisplatin-sensitive and -resistant human hepatoma cell lines. Exp Cell Res 1996; 226:133.PubMedCrossRefGoogle Scholar
  4. 4.
    Jong S, Zulstra JG, Bosscha HT, Mulder NH, et al. Detection of DNA cross-links in tumor cells with the ethidium bromide fluorescence assay. Int J Cancer 1986; 37:557.PubMedCrossRefGoogle Scholar
  5. 5.
    Levy E, Baroche C, Barret JM, et al. Activated ras oncogene and specially acquired resistance to cisplatin in human mammary epithelial cells: induction of DNA cross-links and their repair. Carcinogenesis 1994; 15:845.PubMedCrossRefGoogle Scholar
  6. 6.
    Oude ER, Bakker CKK, Roelofsen H, et al. Hepatology 1993; 17:433.CrossRefGoogle Scholar
  7. 7.
    Ishikawa T, Wright CD, Ishizuka H. GS-X pump is functionally overexpressed in cis-diamminedichloroplatinum (II)-resistant human leukemia HL-60 cells and down-regulated by cell differentiation. J Biol Chem 1994; 269:29085.PubMedGoogle Scholar
  8. 8.
    Bungo M, Ujiwara Y, Kasahara K, et al. Decreased accumulation as a mechanism of resistance to cis-diamminedichloroplatinum (II) in human non-small cell lung cancer cell lines. Relation to DNA damage and repair. Cancer Res 1990; 50:2549.PubMedGoogle Scholar

Copyright information

© Chinese Journal Of Cancer Research 1997

Authors and Affiliations

  • Zhan Maocheng 
    • 1
  • Liu Xuyi 
    • 1
  • Cai Peng 
    • 1
  • Xu Guangwei 
    • 1
  1. 1.School of OncologyBeijing Medical UniversityBeijing

Personalised recommendations