Ovarian and uterine serous cancers are extremely lethal diseases that often present at an advanced stage. The late-stage diagnosis of these patients results in the metastasis of their cancers throughout the peritoneal cavity leading to death. Improving survival for these patients will require identifying therapeutic targets, strategies to target them, and means to deliver therapies to the tumors. One therapeutic target is the protein AXL, which has been shown to be involved in metastasis in both ovarian and uterine cancer. An effective way to target AXL is to silence its expression with small interfering RNA (siRNA). We investigate the ability of the novel siRNA delivery platform, p5RHH, to deliver anti-AXL siRNA (siAXL) to tumor cells both in vitro and in vivo as well as examine the phenotypic effects of this siRNA interference. First, we present in vitro assays showing p5RHH-siAXL treatment reduces invasion and migration ability of ovarian and uterine cancer cells. Second, we show p5RHH nanoparticles target to tumor cells in vivo. Finally, we demonstrate p5RHH-siAXL treatment reduces metastasis in a uterine cancer mouse xenograft model, without causing an obvious toxicity. Collectively, these findings suggest that this novel therapy shows promise in the treatment of ovarian and uterine cancer patients.

卵巢癌和子宫浆液性癌是极其致命的疾病，通常已处于晚期。这些患者的晚期诊断导致癌症在整个腹膜腔内转移，导致死亡。提高这些患者的生存率需要确定治疗靶点、针对这些靶点的策略以及针对肿瘤提供治疗的方法。一种治疗靶点是蛋白质 AXL，它已被证明与卵巢癌和子宫癌的转移有关。靶向 AXL 的有效方法是用小干扰 RNA (siRNA) 沉默其表达。我们研究了新型 siRNA 递送平台 p5RHH在体外和体内将抗 AXL siRNA (siAXL) 递送至肿瘤细胞的能力，并检查了这种 siRNA 干扰的表型效应。首先，我们提出的体外测定显示 p5RHH-siAXL 治疗可降低卵巢癌细胞和子宫癌细胞的侵袭和迁移能力。其次，我们展示了 p5RHH 纳米颗粒在体内靶向肿瘤细胞。最后，我们证明 p5RHH-siAXL 治疗可减少子宫癌小鼠异种移植模型的转移，且不会引起明显的毒性。总的来说，这些发现表明这种新疗法在治疗卵巢癌和子宫癌患者方面显示出希望。