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

作者：Cross Sarah N; Cocco Emiliano; Bellone Stefania; Anagnostou Valsamo K; Brower Stacey L; Richter Christine E; Siegel Eric R; Schwartz Peter E; Rutherford Thomas J; Santin Alessandro D^*

来源：American Journal of Obstetrics and Gynecology, 2010, 203(2): 162.e1.

DOI：10.1016/j.ajog.2010.02.056

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

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.

• 出版日期2010-8