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. ? ? ?
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