2016-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/648203摘要：在婦癌的領域中，卵巢癌逐漸成為一個愈來愈重要的疾病，根據衛生福利部國民健康署的癌症登記報告，卵巢癌的發生率逐年升高，且其死亡率在婦女的惡性腫瘤中名列第一。卵巢癌的預後因子包括腫瘤分期、病理組織型態、惡性化的程度、手術後的殘留腫瘤及對化學治療的反應和抗藥性。基質金屬蛋白酶（MMPs)在癌細胞的侵襲和轉移扮演重要的角色，與癌症患者存活率有關。上皮-間質轉化(EMT)失控則可能促使腫瘤細胞抵抗凋亡作用並增進其侵犯和轉移的能力。化療抗藥性在腫瘤復發與惡化扮演重要的角色，可能機制包括多重抗藥性基因的過度表現、微管蛋白發生變異、運輸蛋白的異常表現、增強的DNA修復作用、細胞凋亡途徑受抑制。由於在我們先前的研究發現，BLU基因甲基化之漿液性卵巢癌患者具有較差的整體存活期及較強的化療抗藥性[1]。在這個研究計劃裡，我們將假設BLU會調控上皮-間質轉化(EMT)，透過基質金屬蛋白酶(MMPs)來影響卵巢癌細胞的侵襲與轉移能力，另一方透過調控紫杉醇或鉑類藥物抗藥性的可能機制，來影響卵巢癌細胞的化療抗藥性，藉由卵巢癌細胞株與小鼠的實驗，進而探討BLU基因在卵巢癌細胞的侵襲能力與化療抗藥性機制中所扮演的可能角色，期望對未來卵巢癌治療提供新的策略。<br> Abstract: Ovarian cancer becomes a more and more important disease gradually in the field of gynecologic malignancies. According to the reports of the cancer registration of the Health Promotion Administration, Ministry of Health and Welfare, the incidence of ovarian cancer increased in recent years and the mortality rate is highest in all gynecologic malignancies in Taiwan. The prognostic parameters for ovarian carcinomas include tumor stage, histological subtype, degree of malignancy, residual tumor after surgical intervention and the response to chemotherapy. Matrix metalloproteinases (MMPs) play an important role in the invasion and metastasis of cancer cells. MMPs are associated with the survival of cancer patients. Dysregulation of epithelial-mesenchymal transition (EMT) may promote anti-apoptosis effects of cancer cells and enhace the abilities of invasion and metastasis. The drug resistance plays an important role in the tumor recurrence and progression. The possible mechanisms include over-expression of multi-drug resistance (MDR), variation of the microtubule, abnormal expression of transporter proteins, enhancement of DNA repair and inhibition of apoptotic pathway.In our previous study, we found that BLU gene methylation was associated with poor prognosis and drug resistance in the patients of epithelial ovarian carcinoma[1]. In the current proposal, we hypothesize that BLU will have an influence on EMT which then regulating the invasion and migration of ovarian cancer cells through the MMPs and chemo-resistance of ovarian cancer cells through the possible mechanisms of the drug resistance of paclitaxel and cisplatin. We will figure out the possible biological functions and the underlying mechanisms of BLU gene in tumor invasion and drug resistance of ovarian carcinoma cells. Through this proposal, we expect to provide new strategies for the managements of ovarian cancer patients in the future.