Analysis of Apigenin in Inhibiting Ovarian Tumorigenesis

描述（由申请人提供）：越来越多的证据表明，活性氧（ROS）的增加和PI3K信号的激活在几种人类癌症中普遍存在。众所周知，水果和蔬菜中的抗氧化剂对肺癌、结肠癌、乳腺癌、前列腺癌、膀胱癌和胃癌有保护作用。我们的初步研究表明，芹菜素抑制卵巢癌细胞增殖和肿瘤生长。芹菜素是一种无毒的生物类黄酮化合物，来自植物和蔬菜。然而，芹菜素预防癌症作用的机制仍有待明确。我们假设芹菜素通过抑制癌细胞中ROS的产生和PI3K/AKT信号传导抑制卵巢肿瘤的生长和血管生成。特异性Aim 1旨在确定apigenin抑制卵巢癌细胞中PI3K和AKT信号通路的机制。我们将分析被芹菜素抑制的上游信号分子，包括ROS和EGFR，导致细胞中PI3K和AKT的抑制。特异性Aim 2旨在确定芹菜素是否抑制卵巢肿瘤发生和血管生成，以及PI3K和AKT是否为芹菜素抑制的影响卵巢肿瘤生长和血管生成的重要下游分子。本研究将有助于发现芹菜素抑制的新信号分子，揭示芹菜素抑制卵巢肿瘤生长和血管生成的机制，为今后芹菜素预防卵巢癌的合理策略奠定基础。

DESCRIPTION (provided by applicant): Accumulating evidence shows that the increase of reactive oxygen species (ROS) and activation of PI3K signaling are commonly observed in several human cancers. It is known that antioxidants from fruits and vegetables have protective effects against lung, colon, breast, prostate, bladder, and stomach cancer. Our preliminary studies demonstrated that apigenin inhibits ovarian cancer cell proliferation and tumor growth. Apigenin is a nontoxic bioflavonoid compound from plants and vegetables. However, the mechanism underlying the cancer prevention effect of apigenin remains to be defined. We hypothesize that apigenin inhibits ovarian tumor growth and angiogenesis by inhibiting ROS production and PI3K/AKT signaling in the cancer cells. Specific Aim 1 is designed to identify the mechanism of apigenin in inhibiting PI3K and AKT signaling in ovarian cancer cells. We will analyze the upstream signaling molecules including ROS and EGFR that are inhibited by apigenin leading to the inhibition of PI3K and AKT in the cells. Specific Aim 2 is designed to determine whether apigenin inhibits ovarian tumorigenesis and angiogenesis, and whether PI3K and AKT are essential downstream molecules inhibited by apigenin for affecting ovarian tumor growth and angiogenesis. This work will identify new signaling molecules inhibited by apigenin, reveal mechanism of apigenin in inhibiting ovarian tumor growth and angiogenesis, and help to establish rational strategies for ovarian cancer prevention using apigenin in the future.