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

Sarah N. Cross, Emiliano Cocco, Stefania Bellone, Valsamo K. Anagnostou, Stacey L. Brower, Christine E. Richter, Eric R. Siegel, Peter E. Schwartz, Thomas J. Rutherford, Alessandro D. Santin

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14 Scopus citations

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 (IC50) 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-IC50 (P = .005) and a 5.37-fold decrease in cisplatin-IC50 (P = .02). When all cell lines were analyzed as a group, chemotherapy agents tested demonstrated lower IC50 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.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume203
Issue number2
DOIs
StatePublished - Apr 22 2010

Keywords

  • HER-2/neu
  • chemoresistance
  • chemosensitivity
  • endometrial neoplasms
  • uterine serous tumors

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