从microRNA角度探讨胰腺癌不同中医证型的分子基础研究

ZHENG, also known as syndrome, is the essence of traditional Chinese medicine (TCM) theory and clinical treatment. ZHENG study has been remaining one the most important research topics in TCM, including TCM for cancer. It has been confirmed that tumor cells do not act in isolation, but rather subsist in a rich microenvironment provided by resident stromal cells. It may be realized that cancer progress is manifested with different ZHENG macroscopically, while it is shown microscopically as alteration of tumor cells and their surrounding microenvironment and the internal environment of the body.In the last study, we confirmed the relationship between ZHENG with CAF and TAM, which partly reveal the molecular basis of ZHENG. In the other clinical study, we found that the expression of microRNA significent differently among different ZHENG.MicroRNA could regulate the expression and function of the CAF and TAM. So, is the microRNA the intermediate links between ZHENG with CAF and TAM, and the molecular basis of ZHENG would be further revealed by microRNA?It worth further study.Therefore, in this study we will establish mouse xenograft pancreatic cancer models with different TCM ZHENG to study the correlation between ZHENG and microRNA in pancreatic cancer. We will also evaluated the correlation between herbal medicine-induced alteration of microRNA under different ZHENG conditions and treatment response. Based on which, combined with ZHENG evaluation in pancreatic cancer patients, we try to unveil the molecular basis of TCM ZHENG in pancreatic cancer.

证是中医学理论和临床治疗的核心，证实质研究是中医肿瘤研究的重要内容。恶性肿瘤发生发展的过程，是肿瘤细胞与其微环境相互作用的过程，该过程宏观表现为中医的证，微观表现为肿瘤微环境变化。我们前一项研究证实了证与微环境中肿瘤相关成纤维细胞（CAF）及巨噬细胞(TAM)的表达及功能相关，部分阐明了证的实质。另一项研究中我们发现不同中医证型间存在microRNA(miR)的表达差异，而miR能调节CAF及TAM的表达及功能。那么中医的证与CAF及TAM的相关性是否通过miR介导，miR的改变能否进一步反应证的实质? 值得进一步研究。所以，本研究拟通过胰腺癌不同中医“证”动物模型，结合胰腺癌患者中医证型研究，明确胰腺癌不同中医证型与miR之间的相关性，并通过不同治则中药干预研究，以期明确胰腺癌不同中医证型下miR变化、及其与中药治疗敏感性的关联，从而进一步揭示胰腺癌中医证型的分子基础。

证是中医学理论和临床治疗的核心，证实质研究是中医肿瘤研究的重要内容。恶性肿瘤发生发展的过程，是肿瘤细胞与其微环境相互作用的过程，该过程宏观表现为中医的证，微观表现为肿瘤微环境变化。我们通过建立具有不同中医证型特点的胰腺癌小鼠模型、收集100例胰腺癌患者证候分型资料及肿瘤组织，并对瘤体间的microRNA表达进行了检测，发现miR-181b、miR-155、miR-301a、 miR-23B等microRNA在不同证型间表达存在差异(P<0.01)。进一步对建立先瘤后证、先证后瘤小鼠，发现在先瘤后证脾虚小鼠中，肿瘤增殖速度、TAM的浸润程度、细胞因子IL-6及p-STAT3表达显著高于其他证型小鼠(P<0.05, P<0.01，P<0.01，P<0.01)；在先证后瘤小鼠中，湿热证小鼠的肿瘤增殖速度、TAM的浸润程度显著高于其他证型小鼠(P<0.05, P<0.05)，细胞因子IL-6及p-STAT3表达显著低于其他证型小鼠(P<0.01，P<0.05)。进一步对证型相对应的中药方剂调节肿瘤miRNA的研究发现，证型相对应的中药对肿瘤组织miR的表达无明显影响。本研究拟通过胰腺癌不同中医“证”动物模型，结合胰腺癌患者中医证型研究，明确胰腺癌不同中医证型与miR之间的相关性，并通过不同治则中药干预研究，明确胰腺癌不同中医证型下miR变化、及其与中药治疗敏感性的关联，揭示胰腺癌中医证型的分子基础。