Higher sensitivity to patupilone versus paclitaxel chemotherapy in primary uterine serous papillary carcinoma cell lines with high versus low HER-2/neu expression in vitro.
OBJECTIVE
To compare the in vitro sensitivity/resistance to patupilone versus paclitaxel in uterine serous papillary carcinoma (USPC) with high versus low HER-2/neu expression.


METHODS
Six primary USPC cell lines, half of which overexpress HER-2/neu at a 3+ level, were evaluated for growth rate and tested for their in vitro sensitivity/resistance to patupilone versus paclitaxel by MTS assays. Quantitative RT-PCR was used to identify potential mechanisms underlying the differential sensitivity/resistance to patupilone versus paclitaxel in primary USPC cell lines.


RESULTS
Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines. Compared to low-expressing cell lines, high HER-2/neu expressors were significantly more sensitive to patupilone than to paclitaxel (P<0.0002). In contrast, there was no appreciable difference in sensitivity to patupilone versus paclitaxel in primary USPC cell lines with low HER-2/neu expression. Higher levels of β-tubulin III (TUBB3) and P-glycoprotein (ABCB1) were detected in USPC cell lines with high versus low HER-2/neu expression (P<0.05).


CONCLUSIONS
USPC overexpressing HER-2/neu display greater in vitro sensitivity to patupilone and higher levels of the patupilone molecular target TUBB3 when compared to low HER-2/neu expressors. Due to the adverse prognosis associated with HER-2/neu overexpression in USPC patients, patupilone may represent a promising novel drug to combine to platinum compounds in this subset of aggressive endometrial tumors.
Paik
Daniel
D
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA.
Cocco
Emiliano
E
Bellone
Stefania
S
Casagrande
Francesca
F
Bellone
Marta
M
Siegel
Eric E
EE
Richter
Christine E
CE
Schwartz
Peter E
PE
Rutherford
Thomas J
TJ
Santin
Alessandro D
AD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D014404:Tubulin / Q000096:biosynthesis / Q000378:metabolism; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D034261:Epothilones; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D014404:Tubulin; C093788:epothilone B