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

Tumour Biol. 2011 Apr;32(2):399-408. doi: 10.1007/s13277-010-0133-6. Epub 2010 Nov 27.


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. 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. Upon acquiring CDDP resistance, tumor markers such as TPA and LDH increased, while proliferative capability of the cells was lowered. 3. The invasion capability was diminished in EICR-If cells, but was increased in EICR-Ia and EICR-II cells. 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. 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. Analyses of cancer- and apoptosis-related genes showed increased expressions of Bcl-2, c-Myc, p53, and ICE in EICR-If cells. 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.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / therapeutic use*
  • Dose-Response Relationship, Drug
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm*
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Female
  • Humans
  • Mitomycin / therapeutic use
  • Neoplasm Invasiveness / pathology
  • Platinum / metabolism


  • Antineoplastic Agents
  • Platinum
  • Mitomycin
  • Doxorubicin
  • Cisplatin