TY - JOUR
T1 - Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro
AU - Cross, Sarah N.
AU - Cocco, Emiliano
AU - Bellone, Stefania
AU - Anagnostou, Valsamo K.
AU - Brower, Stacey L.
AU - Richter, Christine E.
AU - Siegel, Eric R.
AU - Schwartz, Peter E.
AU - Rutherford, Thomas J.
AU - Santin, Alessandro D.
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - HER-2/neu
KW - chemoresistance
KW - chemosensitivity
KW - endometrial neoplasms
KW - uterine serous tumors
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U2 - 10.1016/j.ajog.2010.02.056
DO - 10.1016/j.ajog.2010.02.056
M3 - Article
C2 - 20417484
AN - SCOPUS:77955661117
VL - 203
SP - 162.e1-162.e8
JO - American Journal of Obstetrics and Gynecology
JF - American Journal of Obstetrics and Gynecology
SN - 0002-9378
IS - 2
ER -