RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion
RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion
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DOI：
10.1016/j.canlet.2008.11.010
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发表时间：
2009-04-18
期刊：
影响因子：
9.7
通讯作者：
Kanekura, Takuro
中科院分区：
文献类型：
--
作者：
Kuang, Ye-Hong;Chen, Xiang;Kanekura, Takuro
CD147 （basigin， EMMPRIN）是一种分布广泛的细胞表面糖蛋白，属于Ig超家族。它在恶性肿瘤细胞表面高度表达，促进其侵袭性和耐药。本研究旨在揭示CD147对人口腔鳞癌（SCC）多重耐药（MDR）表型的抗凋亡作用及其可能的途径。本研究的数据显示，通过RT-PCR和Western blot分析，MDR衍生的SCC KB/V细胞系表达的CD147和X-linked inhibitor of apoptosis （XIAP）明显高于其敏感的KB细胞。转染CD147 siRNA下调CD147导致XIAP表达降低。流式细胞分析和电镜观察显示不同细胞凋亡状态与CD147表达相关。此外，通过MTT比色法测定，CD147沉默增加了KB/V对5-氟尿嘧啶的化学敏感性。这些结果表明，抑制CD147和随后的XIAP缺失可能通过增强癌细胞对凋亡的敏感性而具有抗肿瘤作用。2008爱思唯尔爱尔兰有限公司版权所有。
CD147 (basigin, EMMPRIN) is a widely distributed cell surface glycoprotein that belongs to the Ig superfamily. it is highly expressed on the surface of malignant tumor cells to promote their invasiveness and chemo-resistance. The present study aimed to reveal the anti-apoptotic effect of CD147 on the multi-drug resistant (MDR) phenotype of human oral squamous carcinoma cells (SCC) and its possible pathways. Data presented herein showed that MDR derivative SCC KB/V cell line expressed significantly higher CD147 and X-linked inhibitor of apoptosis (XIAP) than its sensitive counterpart KB cells by RT-PCR and Western blot analysis. Down-regulation of CD147 by transfection with CD147 siRNA resulted in decreased XIAP expression. Flow cytometric analysis and electron microscopic observation revealed differential cell apoptotic status related to CD147 expression. Additionally, chemo-sensitivity to 5-fluorouracil of KB/V was increased by CD147 silencing as measured by MTT colorimetric assay. These results suggest that inhibition of CD147 and subsequent XIAP depletion may have an anti-tumor effect through enhancing the susceptibility of cancer cells to apoptosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.