The Effects And Signaling Pathway Of Lpa On Gastric Cancer Cell Proliferation And Its Migration

AIM To study the effects of Lysophosphatidic acid (LPA) on proliferation and migration of gastric cancer cells and to explain its signaling pathway involved in the receptor. It would supply new thought and theoretical basis for the study of gastric cancer mechanism.Contents Gastric cancer cells (BGC-803) were cultured and stimulated by LPA, LPC and compared with Ki16425(An antagonist of LPA1/3receptor) and PTX (Gi protein specificity inhibitor)and PD98059(ERK specificity inhibitor), then their proliferation was observed by MTT assay, and their migration was measured by Boyden chamber.Western blot assay and immunohistochemistry was used to detect the ERK1/2phosphorylation activity of gastric cancer tissues and cells before and after the stimulation with LPA and LPC, at present compared with K116425and PTX.Immunohistochemistry technology was used to detect the expression of ATX in gastric tissue. Gene expression of LPA receptors and Autotaxin was assayed by real-time quantitative PCR. Autotaxin enzyme activity was detected by the method of detecting the absorbance, and determine the affect of LPC-LPA by RNA interference experiment.Results MTT assay showed that both the LPA and LPC stimulated BGC-803 proliferation and migration, which could be inhibited by Ki16425or PTX. Real time quantitative PCR analysis showed that all four receptors of LPA1-4are expressed in BGC-803, among which the expression of LPA1is far higher than other receptors. Western blot analysis showed that LPA, LPC and EGF could stimulate ERK1/2phosphorylation all alone. Both the Ki16425and PTX decreased the expression of p-ERK1/2induced by LPA and LPC, but not by EGF. The gene that encoding Autotaxin was highly expressed in gastric tissues and in BGC-803, and Autotaxin has phospholipase D activity that hydrolyze LPC to LPA. The LPC stimulated BGC-803cells proliferation,and migration were inhibited by siRNA interfering of Autotaxin gene.Conclusions1.The gene that encoding Autotaxin was highly expressed in BGC-803and Autotaxin has phospholipase D activity that hydrolyze LPC to LPA.2.The main extracellular resources of LPA was that Autotaxin could hydrolyze LPC to LPA.3.LPA induced gastric cells proliferation and migration through the LPC-Autotaxin-LPA-LPA1/3-Gi-ERK signaling pathway.4. ATX and LPA1/3receptors are potential targets which can be used in cancer treatment.