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Nanomedicine. 2018 Apr 7;14(4):1395-1405. doi: 10.1016/j.nano.2018.03.005. [Epub ahead of print]

Intraperitoneal nanotherapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin.

Author information

1
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
2
Fairborz Maseeh Department of Mathematics and Statistics, Portland State University, OR, USA.
3
Department of Biochemistry and Redox Biology Center, University of Nebraska, Lincoln, NE, USA; Fred & Pamela Buffett Cancer Center, Omaha, NE, USA.
4
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA. Electronic address: Oleh.Taratula@oregonstate.edu.

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.

KEYWORDS:

DJ-1; cisplatin; combinatorial therapy; ovarian cancer; siRNA

PMID:
29635082
PMCID:
PMC6174103
[Available on 2019-10-07]
DOI:
10.1016/j.nano.2018.03.005

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