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抗RhoC小干扰RNA通过调节KAI1、MMP9和CXCR4的表达来抑制乳腺癌细胞的增殖和侵袭能力。

Anti-RhoC siRNAs inhibit the proliferation and invasiveness of breast cancer cells via modulating the KAI1, MMP9, and CXCR4 expression.

作者信息

Xu Xu-Dong, Shen Han-Bin, Zhu Li, Lu Jian-Qin, Zhang Lin, Luo Zhi-Yong, Wu Ya-Qun

机构信息

Department of Thyroid and Breast Surgery, The Fifth Hospital of Wuhan, Hanyang District.

Department of Oncology.

出版信息

Onco Targets Ther. 2017 Mar 23;10:1827-1834. doi: 10.2147/OTT.S93164. eCollection 2017.

Abstract

Overexpression of RhoC in breast cancer cells indicates poor prognosis. In the present study, we aim to investigate the possible antitumor effects of anti-RhoC small-interfering RNA (siRNA) in inflammatory breast cancer cells. In this study, a specific anti-RhoC siRNA was used to inhibit RhoC synthesis. Transfection of anti-RhoC siRNA into two IBC cells SUM149 and SUM190 induced extensive degradation of target mRNA and led to significant decrease in the synthesis of protein. Anti-RhoC siRNA inhibited cell proliferation and invasion, increased cell apoptosis, and induced cell cycle arrest in vitro. Moreover, the transfection of siRNA increased the expression of KAI1 and decreased the expression of MMP9 and CXCR4 in both mRNA and protein levels. Furthermore, transplantation tumor experiments in BALB/c-nu mice showed that intratumoral injection of anti-RhoC siRNA inhibited tumor growth and increased survival rate. Our results suggested that RhoC gene silencing with specific anti-RhoC siRNA would be a potential therapeutic method for metastatic breast cancer.

摘要

RhoC在乳腺癌细胞中的过表达提示预后不良。在本研究中,我们旨在探讨抗RhoC小干扰RNA(siRNA)对炎性乳腺癌细胞可能的抗肿瘤作用。在本研究中,使用特异性抗RhoC siRNA抑制RhoC合成。将抗RhoC siRNA转染至两种炎性乳腺癌细胞SUM149和SUM190中,诱导靶mRNA广泛降解,并导致蛋白质合成显著减少。抗RhoC siRNA在体外抑制细胞增殖和侵袭,增加细胞凋亡,并诱导细胞周期停滞。此外,siRNA转染在mRNA和蛋白质水平上均增加了KAI1的表达,降低了MMP9和CXCR4的表达。此外,BALB/c-nu小鼠的移植瘤实验表明,瘤内注射抗RhoC siRNA可抑制肿瘤生长并提高生存率。我们的结果提示,用特异性抗RhoC siRNA沉默RhoC基因可能是转移性乳腺癌的一种潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b6/5370064/2e2bde5f1d5c/ott-10-1827Fig1.jpg

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