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

Gynecol Oncol. 2010 Oct;119(1):140-5. doi: 10.1016/j.ygyno.2010.06.024. Epub 2010 Jul 31.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Carcinoma, Papillary / drug therapy*
  • Carcinoma, Papillary / enzymology
  • Carcinoma, Papillary / metabolism
  • Cell Line, Tumor
  • Cystadenocarcinoma, Serous / drug therapy*
  • Cystadenocarcinoma, Serous / enzymology
  • Cystadenocarcinoma, Serous / metabolism
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Epothilones / pharmacology*
  • Female
  • Humans
  • Paclitaxel / pharmacology*
  • Receptor, ErbB-2 / biosynthesis*
  • Tubulin / biosynthesis
  • Tubulin / metabolism
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / enzymology
  • Uterine Neoplasms / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Epothilones
  • Tubulin
  • Receptor, ErbB-2
  • Paclitaxel
  • epothilone B