Tumor Biology

, Volume 32, Issue 2, pp 399–408 | Cite as

Establishment of three cisplatin-resistant endometrial cancer cell lines using two methods of cisplatin exposure

  • Yasukazu Sagawa
  • Atsuya Fujitoh
  • Hirotaka Nishi
  • Hiroe Ito
  • Tamaki Yudate
  • Keiichi Isaka
Research Article


Using the endometrial cancer cell line EI established in our department, we attempted to establish cisplatin (CDDP)-resistant cell lines by incremental exposure and high concentration exposure methods. Three CDDP-resistant cell lines were isolated, which could be distinguished by morphological differences.
  1. 1.

    Upon acquiring CDDP resistance, the cells tended to become small and grow in a floating state. This tendency was especially marked when using incremental exposure method. Using the incremental exposure method, a cell line obtained by isolating and culturing only adherent cells was designated EICR-Ia, and a cell line established by culturing only floating cells was designated EICR-If. A cell line obtained by the high concentration exposure method was designated EICR-II.

  2. 2.

    Upon acquiring CDDP resistance, tumor markers such as TPA and LDH increased, while proliferative capability of the cells was lowered.

  3. 3.

    The invasion capability was diminished in EICR-If cells, but was increased in EICR-Ia and EICR-II cells.

  4. 4.

    Following exposure to CDDP, the intracellular platinum concentrations were markedly elevated in EI and EICR-If cells, whereas the increase was mild in EICR-Ia and EICR-II cells and the concentration was lower than that in parent EI cells.

  5. 5.

    Studies of drug resistance gene expression revealed increased expression of MDR1, GSTπ, and Topo-II in EICR-If cells; increased expression of GSTπ in EICR-II cells; but no expression of any of the genes in EICR-Ia cells.

  6. 6.

    Analyses of cancer- and apoptosis-related genes showed increased expressions of Bcl-2, c-Myc, p53, and ICE in EICR-If cells.

  7. 7.

    Upon acquiring CDDP resistance, sensitivity to mitomycin and adriamycin decreased, but sensitivity to etoposide and 5-fluorouracil increased.


The findings indicate that the mechanisms of CDDP resistance are different in the three cell lines.


Endometrial cancer Cisplatin (CDDP) Multidrug resistance 


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Yasukazu Sagawa
    • 1
  • Atsuya Fujitoh
    • 1
  • Hirotaka Nishi
    • 1
  • Hiroe Ito
    • 1
  • Tamaki Yudate
    • 1
  • Keiichi Isaka
    • 1
  1. 1.Department of Obstetrics and GynecologyTokyo Medical UniversityTokyoJapan

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