Saikosaponin-d: A potential chemotherapeutics in castration resistant prostate cancer by suppressing cancer metastases and cancer stem cell phenotypes
Saikosaponin-d: A potential chemotherapeutics in castration resistant prostate cancer by suppressing cancer metastases and cancer stem cell phenotypes
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柴胡皂苷-d：通过抑制癌症转移和癌症干细胞表型，成为去势抵抗性前列腺癌的潜在化疗药物
DOI：
10.1016/j.bbrc.2016.05.017
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发表时间：
2016
影响因子：
3.1
通讯作者：
Dang Q
中科院分区：
文献类型：
--
作者：
Zhong Di;Zhang Hui-jian;Jiang Yao-dong;Wu Peng;Qi Huan;Cai Chao;Zheng Shao-bin;Dang Qiang;Zheng SB;Dang Q
雄激素剥夺疗法是晚期前列腺癌（PCa）患者的金标准治疗方案，然而，患者最终会发展为去势抵抗性前列腺癌（CRPC）。目前只有少数化疗药物可用于 CRPC。因此，鉴定新药至关重要。在本研究中，我们将根据其作用机制，探索一种用于 CRPC 治疗的新药物 Saikosaponin-d (SSd)。本研究采用代表 CRPC 的 DU145 和 CWR22Rv1 细胞。使用了一系列细胞、生化和分子生物学测定，例如免疫荧光、酶谱分析、球体形成、集落形成和MTT。最后，我们发现SSd可以剂量和时间依赖性地显着抑制PCa细胞的生长，并在长期给药过程中抑制集落形成，还可以抑制其迁移和侵袭能力，同时逆转上皮间质转化（EMT）并抑制MMP2/9的表达和活性。此外，SSd 可以抑制癌症干细胞 (CSC) 表型，例如自我更新能力。从机制上讲，SSd 通过降低 GSK3β 磷酸化来阻断 Wnt/β-catenin 信号通路，从而影响 EMT 和 CSC。这些发现证明了 SSd 靶向 EMT 和 CSC 的抗癌活性机制，表明 SSd 可以成为 CRPC 治疗的有效药物。
Androgen deprivation therapy is the gold standard regimen for advanced Prostate cancer (PCa) patients, nevertheless, patients eventually develop into castration-resistant prostate cancer (CRPC). Currently only a few chemotherapeutics are available for CRPC. Therefore, it is critical for identifying a new drug. In this study, we will explore a new agent, Saikosaponin-d (SSd), for CRPC therapy based on its mechanism of action. DU145 and CWR22Rv1 cells representing CRPC were employed in this study. A series of cell, biochemical, and molecular biologic assays such as Immunofluorescence, Zymography, Sphere formation, Colony formation, and MTT were used. Finally, we find SSd can significantly inhibit the growth of PCa cells in both dose- and time-dependent and suppress the colony formation during a long-term drug administration, it also can inhibit their migration and invasion abilities, which was accompanied by reverse the epithelial-mesenchymal transition (EMT) and suppress MMP2/9 expression as well as activities. Furthermore, SSd can suppress cancer stem cell (CSC) phenotypes such as self-renewal ability. Mechanistically, SSd blocks Wnt/β-catenin signaling pathway by decreasing GSK3β phosphorylation to affect EMT and CSC. These findings demonstrate the mechanism of anti-cancer activity of SSd in targeting EMT and CSC, suggesting SSd can be a potent agent for CRPC therapy.