Antitumor and Antiangiogenic Effects of Aspirin-PC in Ovarian Cancer. Mol Cancer Ther 2016 Dec;15(12):2894-2904
Date
09/18/2016Pubmed ID
27638860Pubmed Central ID
PMC5136300DOI
10.1158/1535-7163.MCT-16-0074Scopus ID
2-s2.0-85008312083 (requires institutional sign-in at Scopus site) 45 CitationsAbstract
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.
Author List
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 AKAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAnimals
Antineoplastic Agents
Apoptosis
Aspirin
Biomarkers
Cell Line, Tumor
Cell Proliferation
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Humans
Hypoxia
Mice
Neovascularization, Pathologic
Ovarian Neoplasms
Phosphatidylcholines
Thromboxanes
Xenograft Model Antitumor Assays
