从肿瘤炎症微环境角度探讨清胰化积方抑制胰腺癌细胞上皮间质转化的分子机制

Epithelial-mesenehymal transition(EMT) is the essential condition of tumor invasion and metastasis.The latest research shows that the tumor inflammation microenvironment can promote tumor cells EMT, especially the infiltration degree of tumor associated macrophage(TAM) and the level of IL-6 in TAM and serum. So the research of targetting on TAM and IL-6 become hot spot. Treatment with QYHJ inhibited cancer cells EMT and down regulated the serum level of IL-6. So we assume that QYHJ could inhibit pancreatic cancer cell EMT in part by reversing tumor-supporting inflammation. To confirm this hypothesis, This study apply the orthotopic model of pancreatic cancer of NOD/SCID mouse, evaluate the effects of QYHJ on the infiltration degree of TAM and the level of IL-6 in TAM and serum, evaluate the effect of IL-6 on pancreatic cancer cells EMT, mobility and invasion, and confirm that TAM is the target cells of QYHJ.

上皮间质转化是肿瘤侵袭、转移不可缺少的必要条件。最新研究表明，肿瘤炎症微环境可以促进肿瘤细胞发生上皮间质转化，尤其肿瘤炎症微环境中的肿瘤相关巨噬细胞浸润程度、促炎症因子IL-6水平。针对肿瘤相关巨噬细胞、IL-6的药物成为目前的研究热点。前期工作结果显示清胰化积方可抑制肿瘤细胞上皮间质转化、抑制荷瘤小鼠血清中IL-6等促炎症因子水平。申请者推测清胰化积方通过改善肿瘤炎症微环境抑制胰腺癌细胞发生上皮间质转化。为证实以上假说，本研究建立NOD/SCID小鼠胰腺原位移植瘤，通过分子生物学技术，探讨清胰化积方对肿瘤相关巨噬细胞浸润程度、肿瘤相关巨噬细胞内促炎症因子IL-6水平、血清中IL-6水平的作用，并进一步验证IL-6对胰腺癌细胞上皮间质转化、运动侵袭的影响，明确肿瘤相关巨噬细胞作为清胰化积方治疗的靶细胞的疗效和可行性，为完善清胰化积方抑制胰腺癌细胞EMT提供有效证据。