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Targeted Oncology
Published in: Targeted Oncology 4/2015

01-12-2015 | Original Research

A combination of the telomerase inhibitor, BIBR1532, and paclitaxel synergistically inhibit cell proliferation in breast cancer cell lines

Authors: Yi Shi, Lin Sun, Ge Chen, Dongyan Zheng, Li Li, Wanguo Wei

Published in: Targeted Oncology | Issue 4/2015

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Abstract

Breast cancer is one of the most significant causes of female cancer death worldwide. Paclitaxel, an extensively used breast cancer chemotherapeutic has limited success due to drug resistance. 2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532), a small molecule pharmacological inhibitor of telomerase activity, can inhibit human cancer cell proliferation as well. Thus, to enhance breast cancer treatment efficacy, we studied the combination of BIBR1532 and paclitaxel in breast cancer cell lines. Cell viability assays revealed that BIBR1532 or paclitaxel alone inhibited proliferation in a dose-dependent manner, and combining the drugs synergistically induced growth inhibition in all breast cell lines tested independent of their p53, ER, and HER2 status. The drug combination also synergistically inhibited colony formation of MCF-7 cells in a dose-dependent manner. Annexin V-PI staining and Western blot assays on PARP cleavage and caspase-8 and caspase-3 revealed that BIBR1532 in combination with paclitaxel was more potent than either agent alone in promoting MCF-7 cell apoptosis. Cell cycle analysis indicated that BIBR1532 induced a G1 phase arrest and paclitaxel arrested cells at the G2/M phase. The drug combination dramatically blocked S cells from entering the G2/M phase. Our results suggest the potential of telomerase inhibition as an effective breast cancer treatment and that used in conjunction with paclitaxel; it may potentiate tumor cytotoxicity.
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Metadata
Title
A combination of the telomerase inhibitor, BIBR1532, and paclitaxel synergistically inhibit cell proliferation in breast cancer cell lines
Authors
Yi Shi
Lin Sun
Ge Chen
Dongyan Zheng
Li Li
Wanguo Wei
Publication date
01-12-2015
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 4/2015
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-015-0364-y

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