肠胃清通过上调p53/Reprimo信号抑制结直肠癌侵袭转移的作用研究

Metastasis is one of the main reasons why therapies fail to treat colorectal cancer (CRC). It was recently found that p53/Peprimo signal is closely related to the invasion and metastasis of cancer, although the mechanism remains elusive. We previously reported that reprimo, an important adjustment factor of p53 signaling, can effectively inhibit occurrence, development, metastasis and invasion. We also showed that TCM ChangWeiQing inhibits the invasion and metastasis of CRC and significantly increases the expression level of Reprimo. Here we postulate that ChangWeiQing may inhibit the invasion and metastasis of CRC by upregulation of p53/Reprimo signaling. We propose to utilize a reprimo gene knockout cell line, as well as human colorectal cancer tissue specimens, reprimo gene knockout mice, and the nude mice metastasis animal model of CRC as models. Then, using CRISPR/Cas9 gene editing technology and small animal imaging technology, we will focus on the molecular mechanism of ChangWeiQing inhibition of the invasion and metastasis via p53/Reprimo signaling. The outcomes of this study well be helpful to reveal the mechanisms of invasion and metastasis of CRC, as well as the specific targets that inhibit CRC, which is both academically and clinically significant. It can provide theoretical guidance and an experimental basis for the prevention and treatment of CRC with Traditional Chinese Medicine.

侵袭转移是结直肠癌治疗失败的主要原因之一，近年研究发现p53/Reprimo信号与肿瘤侵袭转移密切相关。我们前期发现下调Reprimo表达能够抑制结直肠癌的发生发展及侵袭转移；具有健脾解毒功效的中药复方肠胃清能够有效抑制结直肠癌的侵袭转移并显著提高Reprimo的表达水平。我们推测肠胃清可能通过上调Reprimo的表达激活p53信号抑制结直肠癌的侵袭转移。本课题拟以Reprimo基因敲除单克隆细胞株、裸鼠结直肠癌转移动物模型为研究对象，采用CRISPR/Cas9基因编辑技术、小动物活体成像等技术，着重探讨肠胃清对结直肠癌中p53/Reprimo信号的影响，阐明其抑制结直肠癌侵袭转移的分子机理。本研究有助于明确肠胃清抑制结直肠癌的作用靶点，为中医药防治结直肠癌提供理论指导和实验依据。

侵袭转移是结直肠癌治疗失败的主要原因之一，近年研究发现p53/Reprimo信号与肿瘤侵袭转移密切相关。我们前期发现下调Reprimo表达能够抑制结直肠癌的发生发展及侵袭转移；具有健脾解毒功效的中药复方肠胃清能够有效抑制结直肠癌的侵袭转移并显著提高Reprimo的表达水平。我们推测肠胃清可能通过上调Reprimo的表达激活p53信号抑制结直肠癌的侵袭转移。本课题拟以Reprimo基因敲除单克隆细胞株、裸鼠结直肠癌转移动物模型为研究对象，采用CRISPR/Cas9基因编辑技术、小动物活体成像等技术，着重探讨肠胃清对结直肠癌中p53/Reprimo信号的影响，阐明其抑制结直肠癌侵袭转移的分子机理。本研究有助于明确肠胃清抑制结直肠癌的作用靶点，为中医药防治结直肠癌提供理论指导和实验依据