PI3K是一个与细胞生长等密切相关的脂激酶家族，包括4种亚型，其功能有所不同。前列腺癌易转移，尚无有效药物。靶向PI3K为癌症治疗的研究热点，但关于抗前列腺癌转移未见报道。我们的前期工作证明了同时抑制PI3K 4种亚型具有抗前列腺癌转移作用。本课题预实验又显示与其它亚型相比，靶向PI3K beta 亚型具有更显著的抑制前列腺癌细胞的迁移等作用。为此我们假设beta亚型可能在前列腺癌转移中占主导地位，靶向PI3K beta亚型可能通过抑制癌细胞的迁移侵袭和抗血管生成两种机理而产生抗前列腺癌转移作用。为验证此假设，我们通过建立体内外各种前列腺癌转移模型，利用特异性靶向各种PI3K亚型的小分子探针,采用免疫印迹及ELISA等手段从抗癌细胞迁移和抗血管生成两方面系统研究靶向PI3K亚型抗前列腺癌转移的作用和机理。本研究将证明PI3K beta亚型为前列腺癌转移的重要靶点，为前列腺癌治疗提供新的思路。

PI3K (phosphatidylinositol 3-kinase), which consists of 4 isoforms with respective functions, is known to play important roles in cell growth, etc. Advanced prostate cancer is currently not yet curable due to a high rate of metastasis. Favorable antitumor efficacy of targeting PI3K in various solid tumors has been well reported while the anti-metastatic effect remains unknown yet. Our previous study indicated that a pan-PI3K inhibitor which targets all the 4 isoforms of PI3K had potential anti-metastatic effect on prostate cancer via blocking migratin of prostate cancer cells, and inhibiting tumor angiogenesis. Interestingly, our rencent study showed that inhibition against PI3K beta isoform decreased metastatic ability of prostate cancer cells, far more than that againt other 3 respective isoforms did. Therefore, we predict that PI3K beta might play a predominant role in the metastasis of prostate cancer, and targeting PI3K beta might inhibit prostate cancer metastasis via two mechanisms: inhibition of cancer cell migration, adhesion and invasion by downregulating p-Girdin, p-integrin and MMPs, all of which are located downstream of PI3K; and inhibition of tumor angiogenesis via blocking secretion of VEGF by cancer cells. To demonstrate our prediction, we will investigate the anti-metastatic effects of targeting PI3K isofoms on various models in vitro and in vivo with small-molecule probes, by using multiple approaches such as Western blot and ELISA. Our study is expected to demonstrate that PI3K beta is an important molecular target for prostate cancer metastasis, providing a new strategy for the therapy of prostate cancer.