Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NFκB pathway
Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NFκB pathway
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DOI：
10.1016/j.canlet.2007.10.003
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发表时间：
2008-01-18
期刊：
影响因子：
9.7
通讯作者：
Lee, Young Han
中科院分区：
文献类型：
--
作者：
Choi, Byeong Hyeok;Kim, Chang Gun;Lee, Young Han
姜黄素是姜黄的一种成分，在几种动物肿瘤模型中具有抗炎、抗癌和化学预防作用。由mdr基因编码的P-糖蛋白（P-gp）的表达通常与癌细胞对无关化疗药物的多药耐药（MDR）有关。在这里，我们证明，姜黄素下调P-gp在多药耐药L1210/Adr细胞的表达。用mdr 1b基因启动子的一系列5 '缺失构建体转染表明，该序列的-205和+42之间的近端区域负责姜黄素对启动子活性的抑制。这种反应可能与姜黄素抑制磷脂酰肌醇3-激酶（PT 3 K）/Akt/核因子-κ B（NF-κ B）信号通路有关。姜黄素可逆转L1210/Adr细胞的多药耐药。因此，姜黄素可能有助于逆转MDR表型，这可能是由于通过抑制PI 3 K/Akt/NF-κ B信号通路抑制P-gp表达。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Curcumin, a constituent of turmeric, has anti-inflammatory, anti-carcinogenic, and chemopreventive effects in several animal tumor models. The expression of P-glycoprotein (P-gp), encoded by the mdr gene, is often associated with multidrug resistance (MDR) to unrelated chemotherapeutic drugs in cancer cells. Here, we demonstrate that curcumin down-regulates P-gp expression in multidrug-resistant L1210/Adr cells. Transfection with a series of 5'-deleted constructs of the mdr1b gene promoter indicated that a proximal region between -205 and +42 of the sequence was responsible for tile suppression of promoter activity by curcumin. This response might be associated with the inhibition of the phosphatidyinositol 3-kinase (PT3K)/Akt/nuclear factor-kappa B (NF-kappa B) signaling pathway by curcumin. Moreover, curcumin reversed the MDR of the L1210/Adr cells. Thus, curcumin can contribute to the reversal of the MDR phenotype, probably due to the Suppression of P-gp expression via the inhibition of the PI3K/Akt/NF-kappa B signaling pathway. (c) 2007 Elsevier Ireland Ltd. All rights reserved.