OncoTargets and Therapy (Mar 2020)
Omega-3PUFA Attenuates MNU-Induced Colorectal Cancer in Rats by Blocking PI3K/AKT/Bcl-2 Signaling
Abstract
Zhe Huang,1,2,* Chun-An Liu,3,* Peng-Zhu Cai,2 Fei-Peng Xu,2 Wen-Jing Zhu,2 Wei-Wei Wang,2 Hai-Ping Jiang1 1The First Affiliated Hospital, Jinan University, Guangzhou 510000, People’s Republic of China; 2Department of Gastrointestinal Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, People’s Republic of China; 3Department of General Surgery, Ji’an Central Hosipital, Ji’an 343000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hai-Ping JiangThe First Affiliated Hospital, Jinan University, Guangzhou 510000, People’s Republic of ChinaTel +86-13392692225Email [email protected]: Omega 3 polyunsaturated fatty acid (Omega-3PUFA) is one of the essential nutrients for human body involved in intracellular metabolic regulation and cell signaling. Previous studies have shown that Omega-3PUFA is involved in the pathogenesis of digestive system tumors, including colorectal cancer (CRC), however, the effects of Omega-3PUFA on CRC has not been fully elucidated. In the current study, we evaluated whether Omega-3PUFA can alleviate N-methyl-N-nitrosourea(MNU) induced CRC in a rat model and illustrated the potential mechanism.Methods: The effects of Omga-3PUFA on MNU-induced colorectal cancer in rats were analyzed by in vivo experiments. The viability, apoptosis, colony formation and invasion of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry, clone formation assay and transwell invasion assay. The expression of apoptosis-related proteins in CRC cells treated with Omga-3PUFA was detected by Western blotting. Finally, after adding PI3K activator, the viability, apoptosis and protein expression of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry and Western blotting.Results: Our results showed that Omega-3PUFA attenuated MNU-induced CRC in rats and inhibited AKT/Bcl-2 signaling in rats. In addition, Omega-3PUFA inhibited CRC cell proliferation and induces CRC cell apoptosis. Moreover, Omega-3PUFA inhibited CRC cell colony formation and invasion, and inhibited PI3K/AKT/Bcl-2 signaling in CRC cells. Furthermore, The effects of Omega-3PUFA on cell proliferation and apoptosis were inhibited by blocking PI3K/AKT signaling.Conclusion: Omega-3PUFA can attenuate MNU-induced colorectal cancer in rats by blocking PI3K/AKT/Bcl-2 signaling, which suggests that Omega-3PUFA may be a potent agent for CRC treatment.Keywords: Omega-3PUFA, colorectal cancer, PI3K/AKT signaling, apoptosis
