Acquired docetaxel-resistance of prostate cancer (PCa) remains a clinical obstacle due to the lack of effective therapies. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic triterpenic acid isolated from the fragrant gum resin of the Boswellia serrata tree, which has shown intriguing antitumor activity against human cell lines established from PCa, colon cancer, malignant glioma, and leukemia. In this study, we examined the effects of AKBA against docetaxel-resistant PCa in vitro and in vivo as well as its anticancer mechanisms. We showed that AKBA dose-dependently inhibited cell proliferation and induced cell apoptosis in docetaxel-resistant PC3/Doc cells; its IC50 value in anti-proliferation was ∼17 μM. Furthermore, AKBA dose-dependently suppressed the chemoresistant stem cell-like properties of PC3/Doc cells, evidenced by significant decrease in the ability of mammosphere formation and down-regulated expression of a number of stemness-associated genes. The activation of Akt and Stat3 signaling pathways was remarkably enhanced in PC3/Doc cells, which contributed to their chemoresistant stem-like phenotype. AKBA (10-30 μM) dose-dependently suppressed the activation of Akt and Stat3 signaling pathways in PC3/Doc cells. In contrast, overexpression of Akt and Stat3 significantly attenuated the inhibition of AKBA on PC3/Doc cell proliferation. In docetaxel-resistant PCa homograft mice, treatment with AKBA significantly suppresses the growth of homograft RM-1/Doc, equivalent to its human PC3/Doc, but did not decrease their body weight. In summary, we demonstrate that AKBA inhibits the growth inhibition of docetaxel-resistant PCa cells in vitro and in vivo via blocking Akt and Stat3 signaling, thus suppressing their cancer stem cell-like properties.

中文翻译：

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Acetyl-11-keto-β-boswellic acid 通过阻断 Akt 和 Stat3 信号传导，在体外和体内抑制多西紫杉醇耐药的前列腺癌细胞，从而抑制化学耐药性干细胞样特性。

由于缺乏有效的治疗方法，获得性前列腺癌 (PCa) 的多西紫杉醇耐药性仍然是一个临床障碍。Acetyl-11-keto-β-boswellic acid (AKBA) 是一种五环三萜酸，从 Boswellia serrata 树的芳香树胶脂中分离出来，对从 PCa、结肠癌、恶性胶质瘤、和白血病。在这项研究中，我们研究了 AKBA 在体外和体内对多西紫杉醇耐药 PCa 的作用及其抗癌机制。我们发现AKBA剂量依赖性地抑制多西紫杉醇抗性PC3/Doc细胞的细胞增殖并诱导细胞凋亡；其抗增殖的 IC50 值为~17 μM。此外，AKBA 剂量依赖性地抑制了 PC3/Doc 细胞的化学抗性干细胞样特性，由乳腺形成能力的显着降低和许多干性相关基因的下调表达所证明。PC3/Doc 细胞中 Akt 和 Stat3 信号通路的激活显着增强，这有助于它们的化学抗性干细胞样表型。AKBA (10-30 μM) 剂量依赖性地抑制 PC3/Doc 细胞中 Akt 和 Stat3 信号通路的激活。相反，Akt 和 Stat3 的过表达显着减弱了 AKBA 对 PC3/Doc 细胞增殖的抑制。在多西紫杉醇抗性 PCa 同种移植小鼠中，AKBA 处理显着抑制同种移植物 RM-1/Doc 的生长，相当于其人类 PC3/Doc，但并未降低其体重。总之，