癌症治疗已从单一药物转向更多基于机制的靶向方法。近年来，HDAC抑制剂与其他抗癌化学物质的结合在癌症治疗方面取得了令人兴奋的进展。在此，我们通过将二氯乙酸酯与含硒的有效 HDAC 抑制剂连接来开发一种新型前药。还研究了该化合物在治疗前列腺癌中的作用和机制。方法：设计并在温和条件下合成相关前药SeSA-DCA。对该化合物的临床前研究，包括药代动力学、细胞毒性和对前列腺癌细胞系的抗肿瘤作用进行了深入研究，并探讨和讨论了其可能的协同机制。结果：SeSA-DCA在生理条件下表现出良好的稳定性，在肿瘤微环境中可快速分解为DCA和SAHA的硒类似物（SeSAHA）。 CCK-8实验发现SeSA-DCA可以有效抑制多种肿瘤细胞系的增殖，尤其是前列腺癌。在进一步的研究中，我们发现SeSA-DCA还可以抑制前列腺癌细胞系的转移并促进细胞凋亡。在动物水平上，口服 SeSA-DCA 导致肿瘤显着消退，且没有明显毒性。此外，作为一种双分子偶联化合物，SeSA-DCA 在体外和体内均表现出比等摩尔 SeSAHA 和 DCA 的混合物优越得多的功效。我们的研究结果为前列腺癌的临床治疗提供了重要的理论基础。结论：我们的体内和体外结果表明，SeSA-DCA 是一种高效的 PCa 抗肿瘤化合物。与单一疗法相比，它可以有效诱导细胞周期停滞和生长抑制，并抑制PCa细胞系的迁移和转移。 SeSA-DCA 减少异种移植物生长的能力比多西紫杉醇稍好，且没有任何明显的毒性迹象。我们的研究结果为临床前列腺癌治疗提供了重要的理论基础。©作者。

Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer chemicals has produced exciting progress in cancer treatment. Herein, we developed a novel prodrug via the ligation of dichloroacetate to selenium-containing potent HDAC inhibitors. The effect and mechanism of this compound in the treatment of prostate cancer were also studied. Methods: The concerned prodrug SeSA-DCA was designed and synthesized under mild conditions. This compound's preclinical studies, including the pharmacokinetics, cell toxicity, and anti-tumor effect on prostate cancer cell lines, were thoroughly investigated, and its possible synergistic mechanism was also explored and discussed. Results: SeSA-DCA showed good stability in physiological conditions and could be rapidly decomposed into DCA and selenium analog of SAHA (SeSAHA) in the tumor microenvironment. CCK-8 experiments identified that SeSA-DCA could effectively inhibit the proliferation of a variety of tumor cell lines, especially in prostate cancer. In further studies, we found that SeSA-DCA could also inhibit the metastasis of prostate cancer cell lines and promote cell apoptosis. At the animal level, oral administration of SeSA-DCA led to significant tumor regression without obvious toxicity. Moreover, as a bimolecular coupling compound, SeSA-DCA exhibited vastly superior efficacy than the mixture with equimolar SeSAHA and DCA both in vitro and in vivo. Our findings provide an important theoretical basis for clinical prostate cancer treatment. Conclusions: Our in vivo and in vitro results showed that SeSA-DCA is a highly effective anti-tumor compound for PCa. It can effectively induce cell cycle arrest and growth suppression and inhibit the migration and metastasis of PCa cell lines compared with monotherapy. SeSA-DCA's ability to decrease the growth of xenografts is a little better than that of docetaxel without any apparent signs of toxicity. Our findings provide an important theoretical basis for clinical prostate cancer treatment.© The author(s).