Perifosine downregulates MDR1 gene expression and reverses multidrug-resistant phenotype by inhibiting PI3K/Akt/NF-κB signaling pathway in a human breast cancer cell line
Perifosine downregulates MDR1 gene expression and reverses multidrug-resistant phenotype by inhibiting PI3K/Akt/NF-κB signaling pathway in a human breast cancer cell line
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DOI：
10.4149/neo_2012_032
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发表时间：
2012-01-01
期刊：
影响因子：
3
通讯作者：
Li, X.
中科院分区：
文献类型：
--
作者：
Lin, X.;Zhang, X.;Li, X.
P-糖蛋白(P-gp)介导的多药耐药(MDR)是乳腺癌化疗的主要临床障碍。PI3K/Akt通路的下调被认为与肿瘤细胞的多药耐药逆转有关。在这里，我们研究了一种新的Akt抑制剂Perifosine对乳腺癌细胞株MDR表型的逆转作用。本研究用不同浓度的Perifosine处理MCF-7/ADM细胞和MCF-7细胞。结果提示，Perifosine通过下调MCF-7/ADM细胞株P-gp表达，抑制PI3K/Akt/NF-kappa B通路，部分逆转了MCF-7/ADM细胞的MDR。新的Akt抑制剂Perifosine可能是一种很有前途的新药，因为它能够逆转人乳腺癌细胞的多药耐药。
P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is the major clinical impediment to chemotherapy of breast cancers. Down-regulation of PI3K/Akt pathway has been described as related to reversal of MDR in cancer cells. Here, we investigated the reversal effect on MDR phenotype of perifosine, a new Akt inhibitor, in breast cancer cell lines. In this study, MCF-7/ADM cells and MCF-7 cells were treated with different concentrations of perifosine. Our results suggested that perifosine reversed MDR partially by downregulation of P-gp expression and inhibition of PI3K/Akt/NF-kappa B pathway in the MCF-7/ADM cell line. The novel Akt inhibitor perifosine may be a promising new drug due to its ability to reverse MDR in human breast cancer cells.