Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 68, Issue 2, Pages 179-183Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2013.10.003
Keywords
Tamoxifen; Multidrug resistance; PI3K/Akt
Funding
- National Youthful Science Foundation of China [81302148]
- Natural Science Research Foundation of Colleges and Universities in Jiangsu Province [13KJB320019]
- Science Foundation of Post-graduate Cultivation and Innovation Project of Jiangsu Province [CXZZ12_0837]
- Medical Science and Technology Development Foundation
- Suzhou Department of Technology Bureau [YJS0916]
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Multidrug resistance (MDR), mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem limiting successful chemotherapy of gastric cancer. Tamoxifen (TAM), a triphenylethylene nonsteroidal antiestrogen agent, shows broad-spectrum antitumor properties. Emerging studies demonstrated that TAM could significantly reduce the MDR in a variety of human cancers. Here we investigated the effects and possible underlying mechanisms of action of TAM on the reversion of MDR in ER-negative human gastric cancer cells. Our results demonstrated that in MDR phenotype SGC7901/CDDP gastric cancer cells TAM dramatically lowered the IC50 of CDDP, 5-FU and ADM, increased the intracellular Rhodamine123 accumulation and induced G0/G1 phase arrest, while G2/M phase decreased accordingly. Furthermore, at the molecular level, TAM substantially decreased the expression of P-gp, p-Akt and the Akt-regulated downstream effectors such as p-GSK-3 beta, p-BAD, Bcl-XL and cyclinD1 proteins without affecting the expression of t-Akt, t-GSK-3 beta, t-BAD proteins in SGC7901/CDDP cells. Thus, our findings demonstrate that TAM reverses P-gp-mediated gastric cancer cell MDR via inhibiting the PI3K/Akt signaling pathway. (C) 2013 Elsevier Masson SAS. All rights reserved.
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