中文摘要
卵巢癌是妇科恶性肿瘤的首要死因,目前尚缺乏满意的治疗手段。前期临床研究表明扶正消癥方在治疗复发性上皮性卵巢癌(EOC)上具有良好的化疗增效作用。但其具体作用机制尚不明确。单药药理研究表明扶正消癥方的君药能够改善肿瘤微环境。由此我们推测:该方抗肿瘤作用与重建EOC微环境有关。本研究拟从肿瘤相关巨噬细胞(TAMs)为切入点,采用动物模型验证扶正消癥方抗EOC作用,并检测不同干预下EOC组织中TAMs的表型、数量及分布;建立SKOV-3与巨噬细胞共培养体系,探讨扶正消癥方对TAMs表型、吞噬能力及对EOC恶性行为的影响;分析TAMs表型对SKOV-3的EMT诱导作用及扶正消癥方的干预作用,明确EOC免疫微环境促进卵巢癌细胞侵袭、增殖、迁移的可能相关机制,以期为扶正消癥方临床推广应用提供理论依据,更重要的是探索建立临床可行的晚期EOC中医药治疗策略,为延缓及控制晚期EOC复发发挥积极作用。
英文摘要
Ovarian cancer is the leading cause of gynecologic malignant tumors, it is lack of satisfactory treatment. Our previous clinical study has shown that FuZhengXiaoZhengFang combine with chemotherapy in the treatment of recurrent epithelial ovarian cancer (EOC) can improve the overall survive. However, the specific mechanism is unclear. Single-agent pharmacological studies have shown that the main drug of FuZhengXiaoZhengFang can improve the tumor microenvironment.Thus we speculated that the anti-tumor effects of FuZhengXiaoZhengFang may be related to the reconstruction of EOC microenvironment.This study analyzes the tumor associated macrophage (TAMs) as the breakthrough point, we establish nude mouse model of human ovarian carcinoma to verify the effect of FuZhengXiaoZhengFang and detect the phenotype, quantity and distribution of TAMs in EOC ;we establish SKOV-3 and macrophages co-culture system, to explore the impact of FuZhengXiaoZhengFang on TAMs phenotype, phagocytosis and EOC malignant behaviors; We analyse if TAMs phenotype induce EMT of SKOV-3 and the effect of Fuzhengxiaozhengfang, to explore the impossible mechanisms of the immune microenvironment in invasion, proliferation, migration of ovarian cancer. We hope the study can provide the theory basis of Fuzhengxiaozhen for clinical application. More importantly, it is to explore to establish a clinical feasible Traditional Chinese Medicine strategy of advanced EOC treatment.
