中文摘要
结直肠癌的发展、侵袭及转移与肿瘤微环境密切相关,如何改善肿瘤微环境,是防止肿瘤发展、转移的核心问题。肿瘤相关巨噬细胞是肿瘤微环境的重要组成成分,抑制/逆极化肿瘤相关巨噬细胞对于改善肿瘤微环境至关重要。本课题组在临床上使用院内制剂——复方肠泰治疗结直肠癌取得了较好的疗效,前期研究亦发现:复方肠泰能够诱导人结肠癌细胞自噬并分泌自噬体;并且这些自噬体可以极化巨噬细胞。然而这一现象与复方肠泰抗肿瘤作用之间的关系尚不明确。因此,本课题拟以复方肠泰诱导结肠癌细胞分泌自噬体为切入点,运用转基因动物、信号通路磷酸化抗体芯片等多种技术手段,从细胞表型、侵袭与转移相关因子的释放、抗原提呈能力等多方面探讨复方肠泰诱导分泌的自噬体对肿瘤相关巨噬细胞的作用及其机制,并进一步在结肠癌小鼠模型上明确其对肿瘤微环境的影响。为研究复方中药在改善肿瘤微环境,从而减少肿瘤复发与转移的作用提供实验依据和理论基础。
英文摘要
Tumor microenvironment plays a critical role in promoting progression and metastasis of colorectal cancer (CRC). Accumulated evidence suggests tumor-associated macrophages (TAM) are main components of tumor microenvironment, involved in angiogenesis, invasion and metastasis of tumor. Thus, targeting TAM may represent a novel therapeutic strategy for improving tumor microenvironment. In clinical, we use Fufangchangtai (FFCT) to treat colorectal cancer patients. The results show that FFCT can enhance the overall survival rates of CRC patients,keep up the patients’ physical strength and improve the function of immunity. Our findings also indicate that FFCT can induce colorectal tumor cell secreting autophagosomes which can stimulate macrophages. However, the relationship between anti-tumor effect of FFCT and FFCT inducing autophagosomes secretion from tumor cell is unclear. In this study, combined with transgenic mice and microarray technologies, we observe the induced effect on tumor cell autophagy and further investigate whether the effect can inhibit or re-polarize TAM. Also We will examine whether the effect can improve tumor microenvironment. Understanding this issue is critical for developing novel strategies of Compound Traditional Chinese Medicine on tumor therapy.
