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靶向CD147的RNA干扰通过X连锁凋亡抑制蛋白(XIAP)的缺失诱导多药耐药癌细胞凋亡。

RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion.

作者信息

Kuang Ye-Hong, Chen Xiang, Su Juan, Wu Li-Sha, Liao Li-Qiu, Li Dai, Chen Zhe-Sheng, Kanekura Takuro

机构信息

Department of Dermatology, Xiang Ya Hospital, Central South University, 87 Xiang Ya Road, Changsha, Hunan, China.

出版信息

Cancer Lett. 2009 Apr 18;276(2):189-95. doi: 10.1016/j.canlet.2008.11.010. Epub 2008 Dec 20.

Abstract

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.

摘要

CD147(基底膜联蛋白,胞外基质金属蛋白酶诱导因子)是一种广泛分布的细胞表面糖蛋白,属于免疫球蛋白超家族。它在恶性肿瘤细胞表面高度表达,可促进肿瘤细胞的侵袭性和化疗耐药性。本研究旨在揭示CD147对人口腔鳞状细胞癌(SCC)多药耐药(MDR)表型的抗凋亡作用及其可能的途径。本文提供的数据显示,通过逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析,多药耐药性衍生的SCC KB/V细胞系中CD147和X连锁凋亡抑制蛋白(XIAP)的表达明显高于其敏感对应物KB细胞。用CD147小干扰RNA(siRNA)转染下调CD147后,XIAP表达降低。流式细胞术分析和电子显微镜观察揭示了与CD147表达相关的不同细胞凋亡状态。此外,通过噻唑蓝(MTT)比色法检测发现,沉默CD147可增加KB/V对5-氟尿嘧啶的化疗敏感性。这些结果表明,抑制CD147及随后的XIAP减少可能通过增强癌细胞对凋亡的敏感性而产生抗肿瘤作用。

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