Abstract
Ovarian cancer is the most lethal gynecological malignant tumor because of its high recurrence rate. In the present work, in order to find new therapeutic targets, we identified 8480 proteins in thirteen pairs of ovarian cancer tissues and normal ovary tissues through quantitative proteomics. 498 proteins were found to be differentially expressed in ovarian cancer, which involved in various cellular processes, including metabolism, response to stimulus and biosynthetic process. The expression levels of chloride intracellular channel protein 1 (CLIC1) and lectin galactoside-binding soluble 3 binding protein (LGALS3BP) in epithelial ovarian cancer tissues were significantly higher than those in normal ovary tissues as confirmed by western blotting and immunohistochemistry. The knockdown of CLIC1 in A2780 cell line downregulated expression of CTPS1, leading to the decrease of CTP and an arrest of cell cycle G1 phase, which results into a slower proliferation. CLIC1-knockdown can also slow down the tumor growth in vivo. Besides, CLIC1-knockdown cells showed an increased sensitivity to hydrogen peroxide and cisplatin, suggesting that CLIC1 was involved in regulation of redox and drug resistance in ovarian cancer cells. These results indicate CLIC1 promotes tumorgenesis, and is a potential therapeutic target in epithelial ovarian cancer treatment.
Highlights
Ovarian cancer is the fifth leading cause of death and the most lethal gynecological carcinoma in women
In order to find new therapeutic targets, we identified 8480 proteins in thirteen pairs of ovarian cancer tissues and normal ovary tissues through quantitative proteomics. 498 proteins were found to be differentially expressed in ovarian cancer, which involved in various cellular processes, including metabolism, response to stimulus and biosynthetic process
Based on reporter ion ratios (>1.3 or
Summary
Ovarian cancer is the fifth leading cause of death and the most lethal gynecological carcinoma in women. It has an annual new cases of 22280 and mortality of 15500, accounting for 3% new cancer cases and 6% of all cancer deaths in women [1]. It is difficult to diagnose epithelial ovarian cancer (EOC) at early stage because of deep location of the organ in pelvis, over sixty percent of patients are at advanced stage when first diagnosed [2]. The treatment of EOC is improving continuously, the cure rate of patients at advanced stage still remains less than 5-10% and the 5-year survival rate is less than 30% [4]. There is an urgent need to discover promising therapeutic targets of EOC for improving the outcome
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