Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro.
OBJECTIVE
We sought to identify effective chemotherapy regimens against uterine serous papillary adenocarcinoma (USPC).


METHODS
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.


CONCLUSIONS
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.
Cross
Sarah N
SN
Department of Obstetrics, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
Cocco
Emiliano
E
Bellone
Stefania
S
Anagnostou
Valsamo K
VK
Brower
Stacey L
SL
Richter
Christine E
CE
Siegel
Eric R
ER
Schwartz
Peter E
PE
Rutherford
Thomas J
TJ
Santin
Alessandro D
AD
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D018283:Cystadenocarcinoma, Papillary / Q000188:drug therapy / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D011336:Probability; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects* / Q000235:genetics; D012680:Sensitivity and Specificity; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000235:genetics
D016190:Carboplatin; D002945:Cisplatin; D018719:Erb-b2 Receptor Tyrosine Kinases