Medical College of Wisconsin
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Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer. Mol Cancer Ther 2014 Jul;13(7):1750-7

Date

04/24/2014

Pubmed ID

24755199

Pubmed Central ID

PMC4090269

DOI

10.1158/1535-7163.MCT-13-0930

Scopus ID

2-s2.0-84904164280 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

The purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic experiments were conducted in well-established orthotopic mouse models of epithelial ovarian cancer. Antitumor effects were determined on the basis of reduction in mean tumor weight and number of metastatic tumor nodules in the animals. The tumor tissues from these in vivo studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase 3), and microvessel density (CD31). The lowest dose of metronomic regimen (0.5 mg/kg) resulted in significant reduction in tumor growth. The combination of PLGA-PRINT-docetaxel and CH-mEZH2 siRNA showed significant antitumor effects in the HeyA8 and SKOV3ip1 tumor models (P < 0.05). Individual as well as combination therapies showed significant antiangiogenic, antiproliferative, and proapoptotic effects, and combination therapy had additive effects. Metronomic delivery of PLGA-PRINT-docetaxel combined with CH-mEZH2 siRNA has significant antitumor activity in preclinical models of ovarian cancer.

Author List

Gharpure KM, Chu KS, Bowerman CJ, Miyake T, Pradeep S, Mangala SL, Han HD, Rupaimoole R, Armaiz-Pena GN, Rahhal TB, Wu SY, Luft JC, Napier ME, Lopez-Berestein G, DeSimone JM, Sood AK

Author

Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Administration, Metronomic
Animals
Antineoplastic Agents
Cell Line, Tumor
Enhancer of Zeste Homolog 2 Protein
Female
Gene Silencing
Humans
Mice
Mice, Nude
Nanoparticles
Ovarian Neoplasms
Polycomb Repressive Complex 2
RNA, Small Interfering
Randomized Controlled Trials as Topic
Taxoids