Insulin-Like Growth Factor Binding Protein-Related Protein 1 Inhibits HEC-1A Cell Growth By Regulating MEK/ERK Signaling

Background and objectiveEndometrial carcinoma is one of the three largest tumor,which is the most common malignant tumor of female reproductive system. Obesity, high blood pressure, type 2 diabetes as the main performance of the metabolic syndrome is the pathogenesis of endometrial cancer risk factors. Metabolic syndrome is a syndrome that a group of a variety of abnormal metabolic substances caused metabolic disorder, and its pathophysiological foundation is insulin resistance and the subsequent high insulin hematic disease, and then complicated with type 2 diabetes.Insulin growth factor(IGF) system is a central part of the insulin resistance, not only play an important role in energy metabolism is closely associated with the occurrence of a wide variety of tumor development, IGF system including insulin growth factor and its receptors, insulin growth factor binding protein and corresponding hydrolytic enzymes. Insulin like growth factor binding protein-related protein(IGFBP-r P1) is a new member of the IGFBPs super family. When insulin combined with IGFBP- r P1 which decreased its activity, reduced the peripheral blood insulin and and enhanced insulin resistance. Related studies have shown that IGFBP- r P1 is closely related to the occurrence of a wide variety of tumor development, such as colorectal cancer, breast cancer, prostate cancer, et. May play a role as a tumor suppressor genes, but its role in endometrial cancer have not been reported. MEK/ERK signaling pathway is closely related to the development of tumor, the expression in a variety of tumorigenicity disease is raised, pathway activation, cell proliferation and apoptosis. In oral cancer, melanoma, breast cancer, can be found that the excessive activation of signaling pathways ERK1/2. Added Recombinant Human IGFBP-r P1(rh IGFBP-r P1) and PD98059 to HEC-1A cells, and observe the HEC-1A of endometrial cancer cells proliferation, apoptosis, explore the role of IGFBP- r P1 in endometrial carcinoma. MethodsAdded Recombinant Human IGFBP-r P1(rh IGFBP-r P1) and PD98059 to HEC-1A cells, cell proliferation was assessed by CCK-8 method. the levels of total and activated ERK by Western blot. Result1.CCK 8 method shown that addition of rh IGFBP-r P1 blocked proliferation of HEC-1A in a dose-dependent and time-dependent manner. The concentrion of rh IGFBP-r P1 respectively are 2 μ g/ml,4 μ g/ml,8 μ g/ml,16 μ g/ml,and the proliferation inhibition ratio respectively are(16.58±1.72)%,(30.04±0.94)%,(58.74±1.29)%,(81.89±0.87)%,(P<0.05), IC50=6.39μg/ml;4μg/ml r IGFBP-r P1 for HEC-1A proliferation inhibition as extended more and more obvious, its proliferation inhibition ratio of 12 hour, 24 hour, 48 hour, 72 hour respectively are(8.25±2.65)%,(3.98±1.41)%,(24.82±1.90)%,(30.04±0.94)%,(P<0.05).2. The MEK/ERK pathway inhibitor PD98059 can enhance the inhibitory effect of r IGFBP-r P1. r IGFBP-r P1(4 μg/ml) and PD98059(25 umol/L) combination, increased cell proliferation inhibition rate at each time point are respectively increased to(10.04 + 2.71) %,(17.02 + 1.58) %,(28.59 + 2.04) %,(35.29 + 1.12) %(P < 0.05), western blot shown that add rh IGFBP-r P1, the phosphorylation of ERK1/2 were significantly reduced, phosphorylation of ERK1/2 level and rh IGFBP-r P1 are dose dependent. Conclusion1. rh IGFBP- r P1 action in endometrial cancer cells HEC-1 A, the proliferation inhibition rate of HEC-1A present the obvious time and concentration dependence.2. The MEK/ERK pathway inhibitor PD98059 can enhance rh IGFBP-r P1 inhibition, HEC-1A cell proliferation inhibition rate are dose dependent.3.IGFBP-r P1 can inhibit HEC-1A cell proliferation by MEK/ERK signaling pathway.