Reversal effects of Raloxifene on paclitaxel resistance in 2 MDR breast cancer cells

• Published in: Cancer biology & therapy Vol. 16; no. 12; pp. 1794 - 1801
• Main Authors: Xu, Liang, Lei, Jingyu, Jiang, Donghai, Zhou, Lin, Wang, Shu, Fan, Weimin
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.12.2015
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Bone Density Conservation Agents - pharmacology; breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclin B1 - metabolism; Drug Resistance, Neoplasm - genetics; Female; Humans; Mitosis - drug effects; multidrug resistance; paclitaxel; Paclitaxel - pharmacology; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - metabolism; raloxifene; Raloxifene Hydrochloride - pharmacology; Research Paper; multidrug resistance; paclitaxel; breast cancer; raloxifene
• ISSN: 1538-4047; 1555-8576
• DOI: 10.1080/15384047.2015.1095409

Raloxifene hydrochloride (RAL), one of second generation of selective estrogen receptor modulators (SERMs), is usually used in preventing osteoporosis and breast cancer. The present study evaluated whether Raloxifene might sensitize multidrug resistant (MDR) breast cancers to chemotherapies, especially in estrogen receptor negative (ER−) breast cancer. The results showed that RAL could significantly sensitize ER- MDR breast tumors to paclitaxel both in vitro and in vivo. Combination of Raloxifene could significantly enhance paclitaxel-induced cell apoptosis, G2-M arrest as well as inhibition of cell proliferation in MDR tumors. Further studies showed that the combined treatment did not alter P-glycoprotein expression but increased P-gp ATPase activity. These results suggested that raloxifene might be a valuable chemosensitizer agent for breast cancer therapy.