The Relationship Of The Antitumor Activity Of Docosahexaenoic Acid(DHA) And GPR120 Receptor

G protein-coupled receptors belong to the family of membrane protein and are an important way to transmit extracellular signals into the cytoplasm.They mediate a series of responses in the cell,such as hormone secretion,cell proliferation,and apoptosis.Therefore,G protein-coupled receptors are one of the important targets for clinical treatment of diseases.G protein-coupled receptor 120(GPR120),also known as free fatty acid receptor 4(FFAR4),is a family of rhodopsin in G-protein coupled receptors.In recent years,it has been found that GPR120 is involved in the study of its ligands.It induces a variety of physiological activities such as differentiation and maturation of fat cells,insulin secretion,cell proliferation and apoptosis,and anti-inflammatory.It is also an important research target for the treatment of type II diabetes and obesity.G protein-coupled receptor 40(GPR40),also known as free fatty acid receptor 1(FFAR1),is similar in structure to GPR120,with a seven-transmembrane structure of a typical G-protein coupled receptor.Although both can be activated by free fatty acids,the biological functions are not the same.GPR40 is widely distributed in brain,spinal cord and endocrine cells.It has been found that GPR40 signaling activates lung cancer cell proliferation and migration,while GPR120 plays a negative regulatory role.In-depth study of GPR40 and GPR120 functions has important guiding significance for clinical drug delivery.Through ?-oxidation,free fatty acids can provide energy to the body and maintain the normal operation of the living body.They can also act as ligands to activate intracellular or membrane receptors and participate in signal transduction.Both GPR40 and GPR120 can be activated by medium and long chain fatty acids.Docosahexaenoic acid(DHA)is an omega-3 unsaturated fatty acid mainly found in plants and fish oils.It is a ligand for GPR120 and GPR40 and plays an important role in the formation of cranial nerves.Studies have found that DHA inhibits tumor cell proliferation and promotes apoptosis through GPR120,but the role of DHA is not necessarily related to GPR120.The biological function of DHA and its underlying mechanisms remain to be studied.It has been proven that DHA has biological functions of inhibiting tumor proliferation and promoting apoptosis,and GPR120 signaling pathway is closely related to the occurrence and development of various tumors.In addition,DHA is a ligand of GPR120,so thisstudy focus on the biological function of DHA on lung cancer cells and whether DHA exerts a biological effect through the GPR120 receptor.To this end,we focused on the effects of DHA on proliferation,apoptosis,invasion and metastasis of lung cancer cells.We studied the interaction of DHA with GPR120 by using small molecule selective activators and inhibitors.SRB experiments,Transwell experiments,scratch experiments and flow cytometry methods were used to study the biological activity of DHA on H460 lung cancer cell lines.And we studied the changes in DHA activity in the case where the GPR120 receptor was selectively inhibited by AH-7614 or selectively activated by TUG-891.This study found that DHA dose-dependently inhibited the proliferation and migration of H460 lung cancer cells;however,the effect of DHA on apoptosis was not observed.Both the inhibitor AH-7614 and activator TUG-891 slightly enhanced the growth inhibitory effects on DHA as compared to DHA treatment alone.AH-7614 also increased the effect of DHA on invasion inhibition in H460 cells.The above results may indicate that DHA may not play its own special role through GPR120 signaling pathway in H460 cell line.The anti-tumor properties of DHA are needed further investigation.In addition,in order to further study the relationship between DHA and GPR120 receptor,this study also designed and constructed GPR120 knockout and overexpression lung cancer cell line,which lays a foundation for further study of the relationship between DHA and cancer.