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Down-regulation of NTSR3 inhibits cell growth and metastasis, as well as the PI3K-AKT and MAPK signaling pathways in colorectal cancer.
Biochemistry and Cell Biology ( IF 2.9 ) Pub Date : 2020-03-03 , DOI: 10.1139/bcb-2019-0351
Aihua Liu 1 , Zhongfu Zuo 2 , Linlin Liu 3 , Lihua Liu 3
Affiliation  

Colorectal cancer is a common malignancy. NTS receptor 3 (NTSR3) is known to play an important role in several cancers. This study examined the effects of NTSR3 on cell growth and metastasis in colorectal cancer. Western blot analysis, real-time PCR, immunofluorescence staining, MTT, cell cycle assay, cell apoptosis assay, Hoechst staining, caspase-3 and caspase-9 activity assays, cell adhesion assay, wound healing assay, and a Transwell assay were used in this study. We found that NTSR3 was expressed at relatively high levels in the colorectal cancer cell lines SW620 and SW480. NTSR3 knockdown suppressed cell growth and promoted cell apoptosis. Meanwhile, the protein expression levels of cyclinD1, cyclinE1, CDK4, and p-RB were reduced, and the levels of p-P27, P15, P21, cleaved caspase-3, and cleaved caspase-9 protein were increased. Cell invasiveness and cell migration were reduced with knockdown of NTSR3. In addition, our rescue experiments demonstrated that overexpression of the siRNA-resistant alleles of NTSR3 abrogated the NTSR3-siRNA-mediated effects on cell function. Further, down-regulation of NTSR3 inactivated the PI3K-AKT and MAPK signaling pathways. Collectively, these data demonstrate that knockdown of NTSR3 inhibits cell growth and metastasis, as well as the PI3K-AKT and MAPK signaling pathways in colorectal cancer. Thus, our results indicate that NTSR3 is a potential therapeutic target for treating colorectal cancer.

中文翻译:

NTSR3的下调抑制了大肠癌中的细胞生长和转移以及PI3K-AKT和MAPK信号通路。

大肠癌是常见的恶性肿瘤。已知NTS受体3(NTSR3)在几种癌症中起重要作用。这项研究检查了NTSR3对结直肠癌细胞生长和转移的影响。使用了蛋白质印迹分析,实时PCR,免疫荧光染色,MTT,细胞周期测定,细胞凋亡测定,Hoechst染色,caspase-3和caspase-9活性测定,细胞粘附测定,伤口愈合测定和Transwell测定。这项研究。我们发现NTSR3在大肠癌细胞系SW620和SW480中以相对较高的水平表达。NTSR3组合式抑制细胞生长并促进细胞凋亡。同时,cyclinD1,cyclinE1,CDK4和p-RB的蛋白质表达水平降低,而p-P27,P15,P21,裂解的caspase-3和裂解的caspase-9蛋白水平升高。NTSR3基因敲低可降低细胞侵袭性和细胞迁移。此外,我们的救援实验表明,NTSR3的siRNA耐性等位基因的过表达消除了NTSR3-siRNA介导的对细胞功能的影响。此外,NTSR3的下调使PI3K-AKT和MAPK信号通路失活。总体而言,这些数据表明,敲低NTSR3可以抑制大肠癌中的细胞生长和转移以及PI3K-AKT和MAPK信号通路。因此,我们的结果表明NTSR3是治疗结直肠癌的潜在治疗靶标。NTSR3的下调使PI3K-AKT和MAPK信号通路失活。总体而言,这些数据表明,敲低NTSR3可以抑制大肠癌中的细胞生长和转移以及PI3K-AKT和MAPK信号通路。因此,我们的结果表明NTSR3是治疗结直肠癌的潜在治疗靶标。NTSR3的下调使PI3K-AKT和MAPK信号通路失活。总体而言,这些数据表明,敲低NTSR3可以抑制大肠癌中的细胞生长和转移以及PI3K-AKT和MAPK信号通路。因此,我们的结果表明NTSR3是治疗结直肠癌的潜在治疗靶标。
更新日期:2020-03-03
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