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通过小干扰RNA靶向沉默CXCL1可抑制肝细胞癌的肿瘤生长和凋亡。

Targeted silencing of CXCL1 by siRNA inhibits tumor growth and apoptosis in hepatocellular carcinoma.

作者信息

Han Ke-Qi, He Xue-Qun, Ma Meng-Yu, Guo Xiao-Dong, Zhang Xue-Min, Chen Jie, Han Hui, Zhang Wei-Wei, Zhu Quan-Gang, Zhao Wen-Zhao

机构信息

Department of Oncology, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China.

Department of Pharmacy, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China.

出版信息

Int J Oncol. 2015 Dec;47(6):2131-40. doi: 10.3892/ijo.2015.3203. Epub 2015 Oct 13.

Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy and a major cause of cancer-related mortality worldwide. Our previous study shows that chemokine (C-X-C motif) ligand 1 (CXCL1) was upregulated and CXCR1 was downregulated in tumor tissues as compared to peritumor tissues by chemotaxis assay. As the status of CXCL subgroups and their receptors affect progression of HCC, we evaluated potential mechanisms of CXCL1 associated with anticancer effects in HCC based on our previous study. The effects of targeting CXCL1 by RNA interference (RNAi) on the proliferation and apoptosis of CBRH-7919 cells were observed in vitro and in vivo. Additionally, whether CXCL1 knockdown significantly reduce the activity of STAT3, NF-κB and HIF-1 or not were also estimated. RNAi of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice by inhibited cells proliferation and induced apoptosis. In conclusion, these findings suggest that CXCL1 plays critical roles in the growth and apoptosis of HCC. RNAi of CXCL1 inhibits the growth and apoptosis of tumor cells, which indicates that CXCL1 may be a potential molecular target for use in HCC therapy.

摘要

肝细胞癌(HCC)是一种侵袭性恶性肿瘤,也是全球癌症相关死亡的主要原因。我们之前的研究表明,通过趋化性分析,与癌旁组织相比,肿瘤组织中趋化因子(C-X-C基序)配体1(CXCL1)上调,而CXCR1下调。由于CXCL亚组及其受体的状态影响HCC的进展,基于我们之前的研究,我们评估了CXCL1与HCC抗癌作用相关的潜在机制。在体外和体内观察了通过RNA干扰(RNAi)靶向CXCL1对CBRH-7919细胞增殖和凋亡的影响。此外,还评估了CXCL1敲低是否显著降低STAT3、NF-κB和HIF-1的活性。CBRH-7919细胞中CXCL1的RNAi通过抑制细胞增殖和诱导凋亡降低了裸鼠体内肿瘤的生长。总之,这些发现表明CXCL1在HCC的生长和凋亡中起关键作用。CXCL1的RNAi抑制肿瘤细胞的生长和凋亡,这表明CXCL1可能是HCC治疗中的一个潜在分子靶点。

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