Salvianolic acid A reverses paclitaxel resistance in human breast cancer MCF-7 cells via targeting the expression of transgelin 2 and attenuating PI3 K/Akt pathway.

Abstract

Chemotherapy resistance represents a major problem for the treatment of patients with breast cancer and greatly restricts the use of first-line chemotherapeutics paclitaxel. The purpose of this study was to investigate the role of transgelin 2 in human breast cancer paclitaxel resistance cell line (MCF-7/PTX) and the reversal mechanism of salvianolic acid A (SAA), a phenolic active compound extracted from Salvia miltiorrhiza. Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) indicated that transgelin 2 may mediate paclitaxel resistance by activating the phosphatidylinositol 3-kinase (PI3 K)/Akt signaling pathway to suppress MCF-7/PTX cells apoptosis. The reversal ability of SAA was confirmed by MTT assay and flow cytometry, with a superior 9.1-fold reversal index and enhancement of the apoptotic cytotoxicity induced by paclitaxel. In addition, SAA effectively prevented transgelin 2 and adenosine-triphosphate binding cassette transporter (ABC transporter) including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), and breast cancer resistance protein (BCRP) up-regulation and exhibited inhibitory effect on PI3 K/Akt signaling pathway in MCF-7/PTX cells. Taken together, SAA can reverse paclitaxel resistance through suppressing transgelin 2 expression by mechanisms involving attenuation of PI3 K/Akt pathway activation and ABC transporter up-regulation. These results not only provide insight into the potential application of SAA in reversing paclitaxel resistance, thus facilitating the sensitivity of breast cancer chemotherapy, but also highlight a potential role of transgelin 2 in the development of paclitaxel resistance in breast cancer.

• Authors: Jiangxia Cai, Siying Chen, Weipeng Zhang, Xiaowei Zheng, Sasa Hu, Chengsen Pang, Jun Lu, Jianfeng Xing, Yalin Dong
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 21 Issue 12 Pg. 1725-32 (Oct 15 2014) ISSN: 1618-095X [Electronic] Germany
• PMID: 25442283 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier GmbH. All rights reserved.

Chemical References

• Caffeic Acids
• Lactates
• Microfilament Proteins
• Muscle Proteins
• Tagln2 protein, human
• salvianolic acid A
• Proto-Oncogene Proteins c-akt
• Paclitaxel

Topics

• Caffeic Acids (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Gene Knockdown Techniques
• Humans
• Lactates (pharmacology)
• MCF-7 Cells
• Microfilament Proteins (metabolism)
• Molecular Structure
• Muscle Proteins (metabolism)
• Paclitaxel (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)