Abstract 5403: Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer

Purpose: The purpose of this study was to investigate the combined antitumor effects of metronomic docetaxel-containing PLGA-PRINT nanoparticles and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles (CH-mEZH2 siRNA). Method: In vivo dose-finding studies and therapeutic experiments with PLGA-PRINT-docetaxel and CH-mEZH2 siRNA were conducted in well-established orthotopic mouse models of ovarian cancer (HeyA8 and SKOV3ip1). Antitumor effects were quantified through mean tumor weight and tumor nodule counts. Tumor tissues from these studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase-3), and microvessel density (CD31). Result: Dose-finding studies for PLGA-PRINT-docetaxel revealed all doses (0.5, 1.5, 2 mg/kg for metronomic and 20mg/kg for MTD) significantly reduced tumor burden (p Citation Format: Kshipra M. Gharpure, Kevin S. Chu, Charles Bowerman, Takahito Miyake, Sunila Pradeep, Lingegowda S. Mangala, Hee-Dong Han, Rajesha Rupaimoole, Sherry Y. Wu, Heather J. Dalton, Mary E. Napier, Gabriel Lopez-Berestein, Joseph M. DeSimone, Anil K. Sood. Metronomic docetaxel in PRINT nanoparticles and EZH2 silencing have synergistic antitumor effect in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5403. doi:10.1158/1538-7445.AM2014-5403