Comparative evaluation of small-molecule chemosensitizers in reversal of cisplatin resistance in ovarian cancer cells

Anticancer Res. 2012 Sep;32(9):3651-8.

Abstract

Cisplatin-resistance is one of the major challenges in the treatment of epithelial ovarian cancer. Small-molecule chemosensitizers provide a therapeutically feasible approach to overcome cisplatin resistance in ovarian cancer. However, proper selection of chemosensitizer is of prime importance owing to phenotypic differences in cisplatin-resistant ovarian cancers. The resistance reversal activity of chemosensitizers buthionine sulfoximine (BSO), triethylenetetramine (TETA), genistein, rapamycin and colchicine was investigated in various cisplatin-resistant ovarian cancer cells, 2008 C13, CP70 and OVCAR 8 using MTT assays. Cellular accumulation of cisplatin in the presence of chemosensitizers was analyzed by inductively-coupled plasma-mass spectroscopy (ICP-MS). Chemosensitizers exhibited resistance reversal activity in 2008 C13 and CP70 cells in the following order; colchicine> genistein>TETA> rapamycin ≥ BSO (p<0.05), which is in correlation with cellular accumulation of cisplatin. In conclusion, our study demonstrates that resistance reversal activity of chemosensitizers varies with phenotypic behavior of cisplatin-resistant ovarian cancer cells. Data from our study can be utilized to choose a specific chemosensitizer for individualized combination therapy for cisplatin-resistant ovarian cancer.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Buthionine Sulfoximine / administration & dosage
  • Buthionine Sulfoximine / pharmacology
  • CHO Cells
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacokinetics
  • Cisplatin / pharmacology*
  • Colchicine / administration & dosage
  • Colchicine / pharmacology
  • Cricetinae
  • Cricetulus
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Female
  • Humans
  • Isoflavones / administration & dosage
  • Isoflavones / pharmacology
  • Mass Spectrometry / methods
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Sirolimus / administration & dosage
  • Sirolimus / pharmacology
  • Trientine / administration & dosage
  • Trientine / pharmacology

Substances

  • Isoflavones
  • genistin
  • Buthionine Sulfoximine
  • Cisplatin
  • Trientine
  • Colchicine
  • Sirolimus