Involvement of CD147 in regulation of multidrug resistance to P-gp substrate drugs and in vitro invasion in breast cancer cells
Involvement of CD147 in regulation of multidrug resistance to P-gp substrate drugs and in vitro invasion in breast cancer cells
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DOI：
10.1111/j.1349-7006.2007.00487.x
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发表时间：
2007-07-01
期刊：
影响因子：
5.7
通讯作者：
Xu, Zu-De
中科院分区：
文献类型：
--
作者：
Li, Qing-Quan;Wang, Wen-Juan;Xu, Zu-De
过表达p -糖蛋白（P-gp）的多药耐药（MDR）癌细胞在侵袭和转移行为方面表现出差异。我们旨在阐明这一观察结果的机制，并将携带CD147的载体转染到MCF7和MCF7/Adr细胞中。CD147是一种富含肿瘤细胞表面的糖蛋白，可刺激基质金属蛋白酶（MMPs）的产生，特异性shCD147分别进入MCF7和MCF7/Adr细胞。通过体外侵袭试验和3-（4,5-二甲基噻唑-2-酰基）-2,5-二苯基溴化四唑（MTT）试验，我们发现MCF7细胞中CD147的过表达上调MDR1、MMP2和MMP9的转录和表达水平，促进肿瘤细胞转移并使其对P-gp底物药物产生多药耐药。另一方面，在MCF7/Adr细胞中沉默CD147会导致相反的效果。此外，在cd147过表达的克隆中，Erk1/2被观察到高度激活，并且在Erk1/2特异性抑制剂U0126处理后，MDR1、MMP2和MMP9的表达显著降低。因此，CD147可能具有双重作用，因为它在体外对肿瘤侵袭具有内在的刺激作用，同时也增加了对P-gp底物药物的耐药性。
Multidrug resistant (MDR) cancer cells overexpressing P-glycoprotein (P-gp) display variations in invasive and metastatic behavior. We aimed to clarify the mechanism(s) underlying this observation and transfected vectors carrying CD147, a glycoprotein enriched on the surface of tumor cells that stimulates the production of matrix metalloproteinases (MMPs), and specific shCD147 into MCF7 and MCF7/Adr cells, respectively. Using quantitative real-time polymerase chain reaction and Western blot, we found that overexpression of CD147 in MCF7 cells up-regulated MDR1, MMP2, and MMP9 on both transcription and expression levels, which promoted tumor cells metastasis and conferred them multidrug resistance to P-gp substrate drugs, as determined by in vitro invasion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. On the other hand, silencing of CD147 in MCF7/Adr cells led to the opposite effect. Moreover, Erk1/2 in CD147-overexpressing clones were observed to be highly activate and after treatment with U0126, an Erk1/2-specific inhibitor, the expression of MDR1, MMP2 and MMP9 were decreased significantly. Thus, CD147 may assume a dual role, since it had intrinsic stimulative effects on tumor invasion in vitro as well as increasing resistance to P-gp substrate drugs.