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五味子乙素通过SIRT1相关的SMURF2信号通路减轻结肠炎相关的结直肠癌

Schisandrin B Attenuates Colitis-Associated Colorectal Cancer through SIRT1 Linked SMURF2 Signaling.

作者信息

Pu Zhichen, Zhang Weiwei, Wang Minhui, Xu Maodi, Xie Haitang, Zhao Jun

机构信息

Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P. R. China.

Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu 241001, P. R. China.

出版信息

Am J Chin Med. 2021;49(7):1773-1789. doi: 10.1142/S0192415X21500841. Epub 2021 Oct 9.

Abstract

Colon cancer, a common type of malignant tumor, seriously endangers human health. However, due to the relatively slow progress in diagnosis and treatment, the clinical therapeutic technology of colon cancer has not been substantially improved in the past three decades. The present study was designed to investigate the effects and involved mechanisms of schisandrin B in cell growth and metastasis of colon cancer. C57BL/6 mice received AOM and dextran sulfate sodium. Mice in treatment groups were gavaged with 3.75-30 mg/kg/day of schisandrin B. Transwell chamber migration, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, immunoprecipitation (IP) and immunofluorescence were conducted, and HCT116 cell line was employed in this study. Data showed that schisandrin B inhibited tumor number and tumor size in the AOD+DSS-induced colon cancer mouse model. Schisandrin B also inhibited cell proliferation and metastasis of colon cancer cells. We observed that schisandrin B induced SMURF2 protein expression and affected SIRT1 and . SMURF2 interacted with SIRT1 protein, and there was a negative correlation between SIRT1 and SMURF2 expressions in human colorectal cancer. The regulation of SMURF2 was involved in the anticancer effects of schisandrin B in both and models. In conclusion, the present study revealed that schisandrin B suppressed SIRT1 protein expression, and SIRT1 is negatively correlated with the induction of SMURF2, which inhibited cell growth and metastasis of colon cancer. Schisandrin B could be a leading compound, which will contribute to finding novel potential agents and therapeutic targets for colon cancer.

摘要

结肠癌是一种常见的恶性肿瘤,严重危害人类健康。然而,由于诊断和治疗进展相对缓慢,结肠癌的临床治疗技术在过去三十年中并未得到实质性改善。本研究旨在探讨五味子醇甲对结肠癌细胞生长和转移的影响及其作用机制。C57BL/6小鼠接受氧化偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)处理。治疗组小鼠每天灌胃给予3.75 - 30 mg/kg的五味子醇甲。进行了Transwell小室迁移实验、酶联免疫吸附测定(ELISA)、蛋白质免疫印迹分析、免疫沉淀(IP)和免疫荧光实验,并采用了HCT116细胞系。数据显示,五味子醇甲在AOM + DSS诱导的结肠癌小鼠模型中抑制了肿瘤数量和肿瘤大小。五味子醇甲还抑制了结肠癌细胞的增殖和转移。我们观察到五味子醇甲诱导了SMURF2蛋白表达,并影响了SIRT1。SMURF2与SIRT1蛋白相互作用,在人类结直肠癌中SIRT1和SMURF2表达呈负相关。SMURF2的调控参与了五味子醇甲在体内和体外模型中的抗癌作用。总之,本研究表明五味子醇甲抑制SIRT1蛋白表达,且SIRT1与SMURF2的诱导呈负相关,这抑制了结肠癌细胞的生长和转移。五味子醇甲可能是一种先导化合物,将有助于寻找结肠癌的新型潜在药物和治疗靶点。

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