Role of CXCL12-CXCR4 axis in ovarian cancer metastasis and CXCL12-CXCR4 blockade with AMD3100 suppresses tumor cell migration and invasion in vitro (Retracted Article)
Role of CXCL12-CXCR4 axis in ovarian cancer metastasis and CXCL12-CXCR4 blockade with AMD3100 suppresses tumor cell migration and invasion in vitro (Retracted Article)
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DOI：
10.1002/jcp.27163
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发表时间：
2019-04-01
影响因子：
5.6
通讯作者：
Chen, Yan-Nan
中科院分区：
文献类型：
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作者：
Liu, Yan;Ren, Chen-Chen;Chen, Yan-Nan
卵巢癌（OC）是一种致命的妇科肿瘤，其死亡率居首位。 CXCL12及其受体趋化因子受体4（CXCR4）被发现在OC中高表达，并通过影响肿瘤细胞增殖和侵袭而促进疾病进展。在本研究中，我们旨在探讨 AMD3100（一种选择性 CXCR4 拮抗剂）阻断 CXCL12-CXCR4 轴是否对 OC 的进展有影响。在OC基因表达芯片基因表达综合数据库的基础上，通过微阵列分析筛选OC差异表达基因。收集OC（非转移性和转移性）和正常卵巢组织，测定CXCL12和CXCR4的表达量。引入一系列 AMD3100、针对 CXCR4 的 shRNA 和 pCNS-CXCR4 来治疗具有最高 CXCR4 的 CAOV3 细胞。细胞活力、细胞凋亡、迁移和侵袭均被评估。微阵列分析筛选出OC中CXCL12-CXCR4的差异表达。 CXCL12和CXCR4在OC组织中表达增加，特别是在转移性OC组织中。 AMD3100 或 shRNA 下调 CXCR4 在抑制 CAOV3 OC 细胞系的细胞增殖、迁移和侵袭同时促进细胞凋亡方面具有关键作用。 CXCR4过表达对OC细胞的增殖和侵袭能力具有显着的促进作用。这些结果证实，AMD3100 阻断 CXCL12-CXCR4 轴可抑制 OC 细胞的生长。抑制 CXCL12-CXCR4 轴的抗肿瘤作用为 CXCL12-CXCR4 轴作为 OC 治疗靶点提供了临床前验证。
Ovarian cancer (OC) is a lethal gynecologic tumor, which brings its mortality to the head. CXCL12 and its receptor chemokine receptor 4 (CXCR4) have been found to be highly expressed in OC and contribute to the disease progression by affecting tumor cell proliferation and invasion. Here, in this study, we aim to explore whether the blockade of CXCL12-CXCR4 axis with AMD3100 (a selective CXCR4 antagonist) has effects on the progression of OC. On the basis of the gene expression omnibus database of OC gene expression chips, the OC differentially expressed genes were screened by microarray analysis. OC (nonmetastatic and metastatic) and normal ovarian tissues were collected to determine the expressions of CXCL12 and CXCR4. A series of AMD3100, shRNA against CXCR4, and pCNS-CXCR4 were introduced to treat CAOV3 cells with the highest CXCR4 was assessed. Cell viability, apoptosis, migration, and invasion were all evaluated. The microarray analysis screened out the differential expression of CXCL12-CXCR4 in OC. CXCL12 and CXCR4 expressions were increased in OC tissues, particularly in the metastatic OC tissues. Downregulation of CXCR4 by AMD3100 or shRNA was observed to have a critical role in inhibiting cell proliferation, migration, and invasion of the CAOV3 OC cell line while promoting cell apoptosis. Overexpressed CXCR4 brought significantly promoting effects on the proliferation and invasiveness of OC cells. These results reinforce that the blockade of CXCL12-CXCR4 axis with AMD3100 inhibits the growth of OC cells. The antitumor role of the inhibition of CXCL12-CXCR4 axis offers a preclinical validation of CXCL12-CXCR4 axis as a therapeutic target in OC.