PDCD4抑制细胞自噬对卵巢癌恶性行为的影响及分子机制

项目名称： PDCD4抑制细胞自噬对卵巢癌恶性行为的影响及分子机制

项目编号： No.81202069

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 张霞

作者单位： 青岛大学

项目金额： 23万元

中文摘要： 自噬在肿瘤的发生发展过程中发挥重要作用，可以使肿瘤细胞在营养缺乏的情况下存活并且抵抗化放疗，抑制自噬可以增强肿瘤的治疗效果,降低肿瘤的复发。PDCD4是近年来发现的抑癌基因，我们在前期研究中发现PDCD4在卵巢癌中表达明显下调甚至缺失， PDCD4 表达的上调可明显抑制卵巢癌细胞的生长及成瘤能力，增强卵巢癌细胞的化疗敏感性,但其确切的作用机制尚不清楚。令人振奋的是，我们发现PDCD4可以抑制卵巢癌细胞自噬的发生，提示PDCD4可能通过抑制卵巢癌细胞自噬进而发挥其抑癌基因的作用。本课题拟通过体内外实验，在PDCD4过表达和沉默表达两个体系中证明PDCD4可以通过抑制卵巢癌细胞自噬进而抑制其恶性增殖，增强其化疗敏感性，并且深入阐明其作用的分子机制。通过本研究的完成，不仅为PDCD4功能的研究提供新的思路，并且为在临床上改善卵巢癌的治疗方案有重要的潜在应用价值。

中文关键词： 程序性凋亡因子4；自噬；细胞增殖；肿瘤；分子机制

英文摘要： Autophagy plays important roles in tumorigenesis and cancer development. In normal cells, autophagy clean up damaged organelles and malfunctioned proteins to prevent the cells from becoming cancerous. In cancer cells, autophagy may help them survive stresses, resulting in enhanced malignancy or recurrence after therapy. In addition, autophagy may promote tumor cell survival during chemotherapy or radiation, and prompt disruption of autophagy pathway could be an efficient approach to extend the therapeutic benefits and reduce the incidence of cancer recurrence. PDCD4 (programmed cell death 4) is new tumor suppressor, which can inhibit tumor growth through suppressing protein translation and signal transduction. In previous study, we have found that PDCD4 expression was significantly decreased or lost in ovarian cancer, overexpression of PDCD4 can inhibit malignant proliferation and enhance the chemosensitivity of ovarian cancer cells in vitro and in vivo. However, the exact mechanism of PDCD4 is unclear. More interesting, we found that PDCD4 could inhibit autophagy of ovarian cancer cells, which suggested that PDCD4 could suppress ovarian cancer progression may through inhibiting autophagy. This project aims to test our hypothesis that PDCD4 can inhibit malignant proliferation and enhance the chemosensitivity by

英文关键词： PDCD4；autophagy；cell proliferation；neoplasm；molecular mechanism