Department of Gynecology, Jining No. 1 People's Hospital, Jining, Shandong, China.
Department of Interventional Radiology, Qingdao Hospital of Traditional Chinese Medicine, Qingdao, Shandong, China.
Naunyn Schmiedebergs Arch Pharmacol. 2019 Dec;392(12):1477-1489. doi: 10.1007/s00210-019-01687-2. Epub 2019 Jul 10.
Ovarian cancer is a common human malignancy of the female reproductive system. However, chemotherapy has been proven to have limited effectiveness in a majority of patients. Resibufogenin (RB) is a major active ingredient in cinobufacini, which has been used in the treatment of human malignancies as adjunct agents. This study was designed to examine the anti-cancer effect of RB and the underlying mechanisms in ovarian cancer. Our results showed that RB treatment resulted in cell death, cell cycle arrest, and apoptosis in ovarian cancer cells. The anti-growth and pro-apoptotic effects of RB were also validated in xenograft mice models. Proteomics analysis indicated that RB was able to alter the expressions of several genes, which were involved in the regulation of glycolysis. The suppression effect of RB in the glycolysis pathway of ovarian cancer cells was validated by decreased glucose consumption, lactate production, and extracellular acidification rate (ECAR). We proposed that PIM1 functioned as the key target that mediated the anti-cancer effect of RB against ovarian cancer cells. Our results have revealed that RB downregulated PIM1 in ovarian cancer cells and its downstream genes involved in glycolysis. Moreover, our results indicated that the anti-growth activities and suppressing effect of RB on glycolysis were enhanced significantly by PIM1 knockdown but was attenuated by ectopic PIM1 expression. This provided evidence to support the role of PIM1 in the anti-cancer activities of RB.
卵巢癌是女性生殖系统常见的恶性肿瘤。然而，化疗已被证明对大多数患者的疗效有限。沙蟾毒精是华蟾素的主要活性成分之一，已被用作治疗人类恶性肿瘤的辅助药物。本研究旨在探讨沙蟾毒精对卵巢癌细胞的抗癌作用及其作用机制。我们的结果表明，沙蟾毒精处理导致卵巢癌细胞死亡、细胞周期停滞和凋亡。沙蟾毒精在异种移植小鼠模型中的抗生长和促凋亡作用也得到了验证。蛋白质组学分析表明，沙蟾毒精能够改变参与糖酵解调控的几个基因的表达。沙蟾毒精对卵巢癌细胞糖酵解途径的抑制作用通过降低葡萄糖消耗、乳酸生成和细胞外酸化率（ECAR）得到验证。我们提出 PIM1 作为介导沙蟾毒精对卵巢癌细胞抗癌作用的关键靶标。我们的结果表明，沙蟾毒精在卵巢癌细胞中下调了 PIM1 及其下游参与糖酵解的基因。此外，我们的结果表明，PIM1 敲低显著增强了沙蟾毒精的抗生长活性和对糖酵解的抑制作用，而外源性 PIM1 表达则减弱了这种作用。这为 PIM1 在沙蟾毒精抗癌活性中的作用提供了证据支持。
