2016-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/657503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。基質金屬蛋白酶在癌細胞的侵襲和轉移扮演重要的角色，上皮-間質轉化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。我們先前的研究發現，DOCK4 基因表現異常之卵巢癌患者具有較差的整體存活期。在這個研究計劃裡，我們將假設DOCK4 會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，並經由調控上皮-間質轉化或透過基質金屬蛋白酶來影響卵巢癌細胞的侵襲與轉移能力，藉由卵巢癌細胞株與小鼠的實驗，進而探討DOCK4 在卵巢癌細胞的化療抗藥性機制與腫瘤侵襲轉移能力中所扮演的角色，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 ofgynecologic malignancies. According to the reports of the cancer registration of the HealthPromotion Administration, Ministry of Health and Welfare, the incidence of ovarian cancerincreased 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, degreeof malignancy, residual tumor after surgical intervention and the response to chemotherapy. Matrixmetalloproteinases (MMPs) play an important role in the invasion and metastasis of cancer cells.Dysregulation of epithelial-mesenchymal transition (EMT) may promote anti-apoptosis effects ofcancer cells and enhance the abilities of invasion and metastasis. The drug resistance plays animportant role in the tumor recurrence and progression. The possible mechanisms includeover-expression of multi-drug resistance, variation of the microtubule, abnormal expression oftransporter proteins, enhancement of DNA repair and inhibition of apoptotic pathway.Our previous study found that aberrant DOCK4 expression was associated with poor prognosisin the patients of epithelial ovarian carcinoma. In the current proposal, we hypothesize that DOCK4will have an influence on chemo-resistance of ovarian cancer cells through the possiblemechanisms of the drug resistance of paclitaxel and cisplatin and the invasion and migration ofovarian cancer cells through regulating EMT or MMPs. We will figure out the possible biologicalfunctions and the underlying mechanisms of DOCK4 gene in drug resistance and tumor invasion ofovarian carcinoma cells. It will provide new strategies for the managements of ovarian cancerpatients.卵巢癌DOCK4抗藥性侵襲轉移ovarian cancerDOCK4drug resistanceinvasionmetastasis