中华医学杂志（英文版）2008，Vol.121Issue(20)：1975-1979,5.
Paclitaxel-doxorubicin sequence is more effective in breast cancer cells with heat shock protein 27 overexpression
Paclitaxel-doxorubicin sequence is more effective in breast cancer cells with heat shock protein 27 overexpression
SHI Peng 1WANG Ming-ming 1JIANG Li-yu 1LIU Huan-tao 1SUN Jing-zhong2
作者信息
- 1. Department of General Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China
- 2. Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China
- 折叠
摘要
Abstract
Background Cancer cells with overexpression of heat shock protein 27 (HSP27) are resistant to chemotherapeutic drug doxorubicin (Dox). Paclitaxel (Pacl) was reported to suppress HSP27 expression in ovarian and uterine cancer cells. The purposes of this study were to investigate whether Pacl inhibits the expression of HSP27 in breast cancer cells, whether Pacl can sensitize breast cancer cells with HSP27 overexpression to Dox, and to define a more effective schedule for the combination of Dox with Pacl.Methods The HSP27 high-expressing human breast cancer cell lines, MCF-7 and MDA-MB-435, and the HSP27 low-expressing cell line, MDA-MB-231, were used in this study. The level of HSP27, topoisomerase (Topo) Ha and β expression were assessed by Western blotting. The cytotoxic activities of Dox, Pacl and combination of these two drugs were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometric assays. Results Pacl (0.1 umol/L) inhibited HSP27 expression by approximately 2-fold in MCF-7 and MDA-MB-435 cells, while up-regulating the level of topo lla and β. In contrast, expression of HSP27 in MDA-MB-231 did not change significantly following Pacl treatment. There were synergistic effects in both treatment sequences (Pacl-Dox and Dox-Pacl) when Pacl was combined with Dox. Compared with those treated with the Dox-Pacl sequence, the Pacl-Dox sequence had a stronger effect in cancer cells with HSP27 overexpression, as MCF-7 and MDA-MB-435 treated with the Pacl-Dox sequence had lower viabilities and a higher apoptotic rate.Conclusions Paclitaxel significantly decreases the level of HSP27 in breast cancer cells overexpressing HSP27. In combination therapies, the Pacl-Dox sequence is more effective in clearing breast cancer cells with high HSP27 expression compared with the Dox-Pacl sequence.关键词
apoptosis/doxorubicin/heat shock protein 27/paclitaxel/drug resistanceKey words
apoptosis/doxorubicin/heat shock protein 27/paclitaxel/drug resistance分类
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SHI Peng,WANG Ming-ming,JIANG Li-yu,LIU Huan-tao,SUN Jing-zhong..Paclitaxel-doxorubicin sequence is more effective in breast cancer cells with heat shock protein 27 overexpression[J].中华医学杂志（英文版）,2008,121(20):1975-1979,5.
