人参皂苷CK基于PLA2G16-Hippo通路抑制大肠癌进展的机制研究

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中文摘要
大肠癌(CRC)是临床高发的恶性肿瘤。从天然药物中发现有效抗肿瘤物质已成重要研究方向。人参皂苷CK(GCK)认为是潜在的有效抗肿瘤药物,但其在CRC治疗中的作用及机制尚未阐明。我们前期通过TCGA数据库和RNA-seq发现脂质代谢基因PLA2G16在CRC中作为癌基因通过Hippo通路促进CRC的进展。通过分子对接实验发现GCK是PLA2G16活性的抑制剂,进一步发现其可抑制PLA2G16的蛋白表达和下游COX1/COX2/PEG2等多个细胞因子的活性,提示PLA2G16可能是GCK治疗CRC的一个重要靶基因。本项目拟从分⼦、细胞、组织及动物等多层次并利用CRISPR/Cas9、COIP、GST pull down等技术来明确GCK 对PLA2G16-Hippo通路的调控作用,揭示GCK抑制CRC进展的作用机制。本研究将为GCK的抗肿瘤利用提供理论依据,为CRC的治疗提供新的药物和新靶点。
英文摘要
Colorectal cancer (CRC) is a high incidence of clinical malignancy. The discovery of effective antitumor substances from natural drugs has become an important research direction. Ginsenoside CK (GCK) is a potential anti-tumor drug with good drug resistance, safety and effectiveness. Currently, the role and mechanism of GCK in the treatment of CRC have not been elucidated. In our previous study, we found that the lipid metabolism gene PLA2G16 is an oncogene of CRC through the TCGA database and RNA-seq technology, which is involved in the occurrence and development of CRC through the Hippo signal pathway. Through molecular docking experiments, it was found that GCK is an inhibitor of PLA2G16 of , and further found that GCK can inhibit the protein expression of PLA2G16 and the activity of multiple cytokines such as COX1/COX2/PEG2, indicated that PLA2G16 may be an important target gene for GCK treatment of CRC. This project intends to clarify the specific regulatory mechanism of PLA2G16 on Hippo pathway from the molecular, cellular, tissue and animal levels by using CRISPR/Cas9, COIP, GST pull down and other technologies, subsequently investigating the role of PLA2G16 in inhibiting the malignant progression of CRC by GCK and revealing the mechanism of GCK inhibiting the development of CRC. This study will provide a theoretical basis for the anti-tumor effect of GCK,and provide a new drug and a new target for the treatment of CRC.
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Targeting PLA2G16, a lipid metabolism gene, by Ginsenoside Compound K to suppress the malignant progression of colorectal cancer.
靶向Ginsenoside化合物K靶向PLA2G16,一种脂质代谢基因,以抑制结直肠癌的恶性进展。
DOI:10.1016/j.jare.2021.06.009
发表时间:2022-03
期刊:Journal of advanced research
影响因子:10.7
作者:Yang L;Zheng L;Xie X;Luo J;Yu J;Zhang L;Meng W;Zhou Y;Chen L;Ouyang D;Zhou H;Tan Z
通讯作者:Tan Z
人参皂苷CK基于脂质代谢基因LPCAT1抑制大肠癌进展的机制研究
- 批准号:2020JJ4124
- 项目类别:省市级项目
- 资助金额:0.0万元
- 批准年份:2020
- 负责人:谭志荣
- 依托单位:
PEPT2在抗血小板聚集新药2094处置中的作用及机理研究
- 批准号:81001471
- 项目类别:青年科学基金项目
- 资助金额:21.0万元
- 批准年份:2010
- 负责人:谭志荣
- 依托单位:
国内基金
海外基金
