大黄素对胰腺癌转移微环境的调控作用及机制

Tumor micro-environment plays an important role in tumor metastasis and recurrence. Our Preliminary studies showed that emodin not only enhanced chemotherapy drugs against pancreatic cancer, but also inhibited the formation of pancreatic cancer neovascularization, But the exact mechanism remains unclear by now. This project attempts to study from many aspects the regulation effect and mechanism of micro-environment of emodin on pancreatic cancer metastasis. In micro-environmental level, to establish a nude mouse model with premetastasis, to explore the impact of the pancreas vascular integrity on pancreatic cancer cells exudate blood vessels, and the survival and proliferation in emodin-regulated micro-environment, to clarify the regulatory function of emodin on the first matastasis of the micro-environment-related factors and pancreatic cancer neovascularization. In vitro, to explore the impact of emodin regulation pancreatic cancer tumor cells TGFβ/Smads signal pathways on the expression of the micro-environment-related factors via application of molecular biology methods. To clarify the regulation mechanism of emodin on pancreatic cancer neovascularization in micro-environment. In mRNA level, to research the effect of specific MicroRNA in which emodin inhibits pancreatic cancer angiogenesis. And through the latest molecular biology technology. To enhance emodin-inhibited angiogenesis effect. The results of study will not only offer reference in research ideas and methods for Chinese traditional medicine for prevention and control of pancreatic cancer matastasis and recurrence, but also promote the popularization and application of the clinical significance of the theory.

肿瘤微环境在肿瘤转移与复发中扮演着重要角色，本课题组前期研究表明，大黄素具有增强化疗药物抗胰腺癌的作用，而且可明显抑制胰腺癌新生血管形成的作用，但其确切机制尚不明确。为此，该项目拟从多层面研究大黄素对胰腺癌转移微环境的调控作用及机制。在微环境水平上，建立前转移裸鼠模型，探讨大黄素调控微环境中胰腺血管完整性对胰腺癌细胞渗出血管、存活及其增殖的影响，阐明大黄素对前转移微环境相关因子及胰腺癌新生血管形成的调控作用。在细胞水平上，应用分子生物学方法探讨大黄素调控胰腺癌肿瘤细胞TGFβ/Smads信号通路对微环境相关因子表达的影响，阐明大黄素对微环境中胰腺癌新生血管的调控机制。在RNA水平上，研究特定MicroRNA在大黄素抑制胰腺癌新生血管形成中所起的作用，大黄素的抑制血管生成的效应。该研究结果将为中药防治胰腺癌转移及复发提供可资借鉴的研究思路与方法，促进临床推广应用具有重要的理论意义。

肿瘤微环境在肿瘤转移与复发中扮演着重要角色，而大黄素被我们前期实验证明具有增强化疗药物抗胰腺癌的作用，而且可明显抑制胰腺癌新生血管形成的作用，但其确切机制尚不明确。为此，本项目从多层面研究了大黄素对胰腺癌转移微环境的调控作用及机制。首先，在微环境水平上，建立前转移裸鼠模型，从体内体外多角度进一步探讨大黄素调控微环境中胰腺血管完整性对胰腺癌细胞渗出血管、存活及其增殖的影响，阐明了大黄素对前转移微环境相关因子及胰腺癌新生血管形成的调控作用。然后，在细胞水平上，应用分子生物学方法探讨大黄素调控胰腺癌肿瘤细胞TGFβ/Smads信号通路对微环境相关因子表达的影响，进一步阐明大黄素对微环境中胰腺癌新生血管的调控机制。最后，在RNA水平上，研究特定MicroRNA在大黄素抑制胰腺癌新生血管形成中所起的作用，大黄素的抑制血管生成的效应。该研究结果为中药防治胰腺癌转移及复发提供可资借鉴的研究思路与方法，促进临床推广应用具有重要的理论意义。