结直肠癌是目前常见的恶性肿瘤之一，近来的研究发现在结肠癌组织内磷酸二酯酶5（PDE5）高表达，可能是结直肠癌潜在的治疗靶点。西地那非是高度选择性PDE5抑制剂，通过升高cGMP水平而导致阴茎海绵体平滑肌松弛，临床上用于治疗男性勃起功能障碍。本课题组的前期工作首次发现西那地非能够直接诱导结直肠癌细胞凋亡，并可能与p53的状态密切相关。那么西地那非是否真的具有抗结直肠癌作用？其可能涉及的分子机制是什么？本研究将采用一系列肿瘤药理学、分子生物学方法和技术，在分子、细胞和动物水平上对这些问题进行一一研究和探讨，以期揭示西那地非抗结直肠癌的作用和机制，这将为开发新的抗肿瘤药物提供新的线索和思路，因此具有重要的意义和价值。

Colorectal cancer is one of common malignant tumor. Recent studies show the phosphodiesterase 5 （PDE5）was highly expressed in the tissue of colorectal cancer, and suggest it could be a novel potential target of colorectal cancer therapy. Sildenafil is a highly selective inhibitor of PDE5, which increases of cGMP resulting in Smooth muscle relaxation of corpus cavernosum, and is used in clinic to treat male erectile dysfunction. Our previous work at the first time showed that sildenafil could induce apoptosis in colorectal cancer cells and its effect might be related with p53. Then is it real that sildenal could antagonize colorectal cancer? What is the mechanism? To answer these questions from molecular， cellular and animal level, this project will use a series of cancer phamarcological, molecular biological methods and technologies. It shows the great value to inspire us for developing the novel anti-cancer drugs and creat new opportunity for cancer chemotherapy.