“延寿因子”Spermidine具有潜在的抗肿瘤作用。我们前期研究发现Spermidine可通过调节HDAC4亚细胞定位，减少胞浆内HDAC4，上调自噬因子MAP1S乙酰化和稳定性，增强自噬，抑制CRPC。同时Spermidine可抑制PPARγ介导的脂肪酸合成，且PPARγ表达受组蛋白乙酰化调控。而ANP32、PP2A和14-3-3是影响HDAC4亚细胞定位的主要因子，且ANP32具有和Spermidine结合的预测位点。因此我们提出科学假说：在前列腺癌中，Spermidine通过ANP32/PP2A/14-3-3调节HDAC4亚细胞定位，促进HDAC4入核，减少胞质HDAC4，稳定MAP1S，促进自噬；同时增加核内HDAC4，抑制PPARγ介导的脂肪酸合成，两者协同抑制CRPC。本研究可阐明Spermidine抑制CRPC的机制，为Spermidine治疗前列腺癌提供理论和实验基础。

“Longevity factor” Spermidine has potential anti-tumor effects. According to our previous research, Spermidine can regulate the subcellular localization of HDAC4 (HDAC4 nucleus import), decrease the level of HDAC4 in cytoplasm, promote the acetylation of MAP1S and increase the stability, enhance the level of autophagy and inhibit CRPC. In addition, Spermidine can inhibit the expression of PPARγ, a fatty acid metabolic regulator, and inhibit the synthesis of fatty acids. Also, the expression of PPARγ is regulated by histone acetylation level. ANP32, PP2A and 14-3-3 are the main factors regulating the subcellular localization of HDAC4. ANP32 has a predicted binding domain to Spermidine. Therefore, we put forward the scientific hypothesis: Spermidine can regulate the subcellular localization of HDAC4 in prostate cancer by regulating ANP32/PP2A/14-3-3, promote the entry of HDAC4 into the nucleus. On the one hand, it can reduce the level of HDAC4 in cytoplasm, stabilize MAP1S, and promote autophagy; on the other hand, it can increase the level of HDAC4 in nucleus, inhibit the expression of PPARγ and the synthesis of fatty acids. Both of them inhibit the occurrence and development of CRPC. This study can clarify the mechanism of Spermidine inhibiting CRPC and provide theoretical and experimental basis for Spermidine in the treatment of prostate cancer.