丹酚酸B抑制LPA诱导的输卵管起源卵巢癌发生发展进程的作用机制研究

The high mortality rate in ovarian cancer patients, especially those of high grade serous carcinoma (HGSC) is mainly due to the diagnosis at a late-stage when the cancer has spread into the peritoneal cavity and metastasized to vital organs. Recently, fimbriae of the fallopian tube is identified as the origin of ovarian cancer. However, there are very few studies on the molecular mechanism of traditional Chinese medicine. Pre-experiments show that salvianolic acid B can inhibit LPA-induced tubal origin of ovarian cancer, but the mechanism has not been explored. We test the hypothesis that salvianolic acid B could inhibit the inflammatory microenvironment and apoptotic effects of tubal origin of ovarian cancer induced by LPA through inflammation related signaling pathway. This study will use experimental methods such as Real-time PCR, western blot, Lentiviral Transfection, flow cytometry, ELISA and Laser Confocal to explore the inhibition of salvianolic acid B on tubal origin of ovarian cancer induced by LPA and the mechanism of inflammation related signaling pathway as well as inflammatory micro-environment through three levels as follows: cell lines, NOD-SCID mouse model and human fallopian tubes ex vivo. This research will clarify that salvianolic acid B inhibit LPA induced tubal origin of ovarian cancer through inflammatory environment protection effect, and provide new ideas and new targets for ovarian cancer prevention and treatment.

分化不良浆液性卵巢癌占绝大多数也是最难以早期诊断及治疗的卵巢癌，卵巢癌起源于输卵管伞端已经证实，但是中药相关的分子机制研究仍知之甚少，预实验表明丹酚酸B可抑制LPA诱导的输卵管起源卵巢癌发生发展进程，初步探讨可能机制为抑制炎症因子造成的炎症微环境以及细胞凋亡作用。因此我们提出假说：丹酚酸B可能通过抑制LPA诱导的炎性微环境以及影响炎症信号通路，达到抑制输卵管起源卵巢癌进展的作用。本研究将通过输卵管上皮永生化细胞株和卵巢癌上皮细胞、NOD-SCID小鼠模型以及人体输卵管离体培养，采用qPCR、Western blot、慢病毒转染、流式细胞术、ELISA以及激光共聚焦等手段探讨丹酚酸B对输卵管起源卵巢癌发生发展的抑制作用，明确炎症相关信号通路以及炎症微环境的作用机制。本研究将阐明丹酚酸B对于LPA作用下输卵管起源卵巢癌炎症微环境下保护作用，为卵巢癌的早期预防和治疗提供新思路和新靶点。