The Effects Of GABA_BR Activation On PI3K/Akt And Ras/Raf/ERK Signal In Breast Cancer Cell MDA-MB-231

GABABreceptors are members of class C family of G protein coupled receptors, andtheir ligand is inhibitory neurotransmitter gamma-aminobutyric acid(GABA) of the centralnervous system. it is widely distributed in the mammalian central nervous system andGABA also exists in various tissues outside the central nervous system. The receptors forGABA include two types which GABAA and GABAC receptors are ionotropic medicatedfast GABA reaction, GABABreceptor is metabotropic which medicated slow GABArecation. GABABreceptors consist of GABAB1and GABAB2subunits and exercise thefunction of the heterodimer. GABAB receptor can regulate proliferation and migration ofvariety tumor cell, but the mechanism is not clear. PI3K/Akt signaling pathway plays animportant role in tumor development and occurrence. PI3Ks(phosphatidylinositol3-kinases)is an important kinase in the intracellular which is divided into three categories: class I,class II and class III, that are composited of various catalytic subunit and regulatorysubunit. Catalytic subunit p110and p110can be activated by receptor tyrosine kinase(RTK), p110γ only be activated by GPCR and the p110β can be activated by RTK orGPCR. PI3K/Akt signaling pathway can promote cell growth, survival and proliferation,which is abnormally activated in tumor cells. The classical mitogen-activated protein kinase(MAPK)pathway (Raf/MEK/ERK), activated by cell surface receptor tyrosine kinases(RTKs) following growth factor binding,regulates cell proliferation. Activation of the Raf/MEK/ERK pathway is a frequent event in different human cancers.In this paper, Investigating GABABreceptors influnce the activation of PI3K/Akt andRaf/MEK/ERK pathway in the human breast cancer cell line MDA-MB-231and granuleneurons in mice cellsare. GABABreceptor specific allosteric modulator CGP7930was usedto treat breast cancer cells MDA-MB-231for a short time, and the result showed theAkt and ERK was activated by GABAB receptors. the breast cancer cell lineMDA-MB-231was treated with GABABreceptor agonist Baclofen and allostericmodulator CGP7930, MTT method show that Baclofen can inhibit the proliferation ofMDA-MB-231cells and cell scratch experiment results show that the CGP7930inhibitedcell migration. At present, it rarely seen GABABreceptor activation reporting on breast cancer cells PI3K/Akt and Raf/MEK/ERK signaling pathway, cell proliferation andmigration.Therefore, which can provides a new theoretical basis and model forGABABR-conjugated anti-tumor drug screening.