The Natural Product Fucoidan Inhibits Proliferation and Induces Apoptosis of Human Ovarian Cancer Cells: Focus on the PI3K/Akt Signaling Pathway

Shuhan Liu,1 Jing Yang,2 Xudong Peng,3 Jingjing Li,4 Cunjing Zhu2 1Department of Reproductive Medicine, Jining First People’s Hospital, Jining 272000, People’s Republic of China; 2Department of Gynecology, Jining First People’s Hospital, Jining 272000, People’s Republic of China; 3Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China; 4Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of ChinaCorrespondence: Cunjing Zhu Tel +86-0537-60566666Email zhucunjing@126.comObjective: Ovarian cancer (OC) is the leading cause of death among gynecological tumors; however, no effective treatment is currently available. Fucoidan, which is extracted from marine algae, has significant anti-cancer effects. The aim of this study was to determine the effects of fucoidan on the proliferation and apoptosis of OC cells through inhibition of the PI3K/Akt signaling pathway.Methods: Human ovarian normal epithelial cells (IOSE80) and human OC cells (SKOV-3, A2780, OVCAR-3, TOV-112D, and Caov-3) were selected to verify the safety of fucoidan at various doses in SKOV-3 and Caov-3 cells as well as a xenograft mouse model using various molecular biology techniques.Results: Fucoidan had no significant effect on normal ovarian epithelial cells, but had significantly inhibited the proliferation of OC cells, induced cell cycle arrest at the G0/G1 phase, increased the proportion of apoptotic cells and expression of pro-apoptotic proteins, and inhibited the expression of PI3K and phosphorylation of Akt, which could be partly rescued by IGF-1.Conclusion: Fucoidan had anti-tumor effects both in vivo and in vitro via a mechanism that is related to the inhibition of the PI3K/Akt signaling pathway.Keywords: ovarian cancer, fucoidan, cell cycle, apoptosis, PI3K/Akt