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

抗 RhoC siRNA 通过调节 KAI1、MMP9 和 CXCR4 表达抑制乳腺癌细胞的增殖和侵袭性

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

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.

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