基于 DJ-1 蛋白 siRNA 介导抑制与低剂量顺铂联合的腹腔内纳米治疗转移性卵巢癌。
Intraperitoneal nanotherapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin.
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
Fairborz Maseeh Department of Mathematics and Statistics, Portland State University, OR, USA.
出版信息
Nanomedicine. 2018 Jun;14(4):1395-1405. doi: 10.1016/j.nano.2018.03.005. Epub 2018 Apr 7.
Abstract
Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth and increasing survival of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated DJ-1 therapy in combination with a low dose of cisplatin completely eradicated ovarian cancer tumors from the mice, and there was no cancer recurrence detected for the duration of the study, which lasted 35 weeks.
摘要
在这里，我们报告了一种基于 DJ-1 蛋白的 siRNA 介导抑制与低剂量顺铂联合的转移性卵巢癌的有效联合治疗。DJ-1 蛋白直接或间接地调节支持和促进卵巢癌细胞存活、生长和侵袭的不同致癌途径。为了评估这种新疗法的潜力，我们设计了一种癌症靶向纳米平台，并验证了该纳米平台递送至腹腔内的 DJ-1 siRNA 可有效下调转移性卵巢癌肿瘤和腹水的 DJ-1 蛋白。体内实验表明，DJ-1 siRNA 单药治疗通过抑制肿瘤生长和提高转移性卵巢癌小鼠的存活率，优于单独使用顺铂。最后，三次 DJ-1 介导的 siRNA 治疗联合低剂量顺铂完全消除了小鼠的卵巢癌肿瘤，在研究期间（持续 35 周）未发现癌症复发。
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