Antitumor and Antiangiogenic Effects of Aspirin-PC in Ovarian Cancer.

Published

Journal Article

To determine the efficacy of a novel and safer (for gastrointestinal tract) aspirin (aspirin-PC) in preclinical models of ovarian cancer, in vitro dose-response studies were performed to compare the growth-inhibitory effect of aspirin-PC versus aspirin on three human (A2780, SKOV3ip1, and HeyA8) and a mouse (ID8) ovarian cancer cell line over an 8-day culture period. In the in vivo studies, the aspirin test drugs were studied alone and in the presence of a VEGF-A inhibitor (bevacizumab or B20), due to an emerging role for platelets in tumor growth following antiangiogenic therapy, and we examined their underlying mechanisms. Aspirin-PC was more potent (vs. aspirin) in blocking the growth of both human and mouse ovarian cancer cells in monolayer culture. Using in vivo model systems of ovarian cancer, we found that aspirin-PC significantly reduced ovarian cancer growth by 50% to 90% (depending on the ovarian cell line). The efficacy was further enhanced in combination with Bevacizumab or B20. The growth-inhibitory effect on ovarian tumor mass and number of tumor nodules was evident, but less pronounced for aspirin and the VEGF inhibitors alone. There was no detectable gastrointestinal toxicity. Both aspirin and aspirin-PC also inhibited cell proliferation, angiogenesis, and increased apoptosis of ovarian cancer cells. In conclusion, PC-associated aspirin markedly inhibits the growth of ovarian cancer cells, which exceeds that of the parent drug, in both cell culture and in mouse model systems. We also found that both aspirin-PC and aspirin have robust antineoplastic action in the presence of VEGF-blocking drugs. Mol Cancer Ther; 15(12); 2894-904. ©2016 AACR.

Full Text

Duke Authors

Cited Authors

  • Huang, Y; Lichtenberger, LM; Taylor, M; Bottsford-Miller, JN; Haemmerle, M; Wagner, MJ; Lyons, Y; Pradeep, S; Hu, W; Previs, RA; Hansen, JM; Fang, D; Dorniak, PL; Filant, J; Dial, EJ; Shen, F; Hatakeyama, H; Sood, AK

Published Date

  • December 2016

Published In

Volume / Issue

  • 15 / 12

Start / End Page

  • 2894 - 2904

PubMed ID

  • 27638860

Pubmed Central ID

  • 27638860

Electronic International Standard Serial Number (EISSN)

  • 1538-8514

Digital Object Identifier (DOI)

  • 10.1158/1535-7163.MCT-16-0074

Language

  • eng

Conference Location

  • United States