Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro

Am J Obstet Gynecol. 2010 Aug;203(2):162.e1-8. doi: 10.1016/j.ajog.2010.02.056. Epub 2010 Apr 24.

Abstract

Objective: We sought to identify effective chemotherapy regimens against uterine serous papillary adenocarcinoma (USPC).

Study design: Six USPC, half of which overexpress HER-2/neu at 3+ level, were evaluated for growth rate and in vitro sensitivity to 14 single-agent chemotherapies and 5 combinations by ChemoFx (Precision Therapeutics Inc, Pittsburgh, PA).

Results: Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines and a lower half maximum inhibitory concentration (IC(50)) when exposed to the majority of single-agent chemotherapies. High HER-2/neu expressors were more sensitive to platinum compounds, manifesting a 5.22-fold decrease in carboplatin-IC(50) (P = .005) and a 5.37-fold decrease in cisplatin-IC(50) (P = .02). When all cell lines were analyzed as a group, chemotherapy agents tested demonstrated lower IC(50) when used in combination than as individual agents.

Conclusion: USPC overexpressing HER-2/neu display greater in vitro sensitivity to platinum compounds when compared to low HER-2/neu expressors. Higher proliferative capability rather than increased drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in USPC.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Carboplatin / pharmacology
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Cystadenocarcinoma, Papillary / drug therapy
  • Cystadenocarcinoma, Papillary / genetics
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / genetics
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Middle Aged
  • Probability
  • Receptor, ErbB-2 / drug effects*
  • Receptor, ErbB-2 / genetics
  • Sensitivity and Specificity
  • Uterine Neoplasms / drug therapy
  • Uterine Neoplasms / genetics

Substances

  • Carboplatin
  • Receptor, ErbB-2
  • Cisplatin