Objective To study the molecular mechanism and biological significance of GPR30 activating HER2 in MCF-7 breast cancer cells with low expresses HER2.Methods Western blot was adopted to examine the phosphorylation of HER2 and the downstream signaling molecular ERK1/2 after 17-β-estradiol(E2),4-OHT(the active metabolite of tamoxifen) or G-1 (the GPR30 agonist) treatment in MCF-7 cells.After different inhibitors such as G-15 (the GPR30 antagonist),AG1478(EGFR tyrosine inhibitor),AG825 (HER2 tyrosine inhibitor),PP2 (Src family kinase inhibitor)or GM6001 (MMP inhibitor) pretreated for 2 h,the phosphorylation of HER2 and ERK1/2 were further analyzed.Finally,the altered migration and invasive capability of MCF-7 cells were detected by Transwell method.Results HER2 and ERK1/2 were activated in MCF-7 cells after E2,4-OHT or G-1 treatment and these changes could be inhibited by G-15,AG1478,AG825,PP2 or GM6001 pretreatment.The enhancement of G-1-induced migration and invasion ability in MCF-7 cells could also be inhibited by those inhibitors too.Conclusion GPR30 promotes the migration and invasion of MCF-7 cells through activating HER2-ERK1/2 signal transduction pathway.

Objective To explore the expression of GPR30,HRG1 and HER2 including the activation status of HER2 (phosphorylated HER2)in invasive ductal breast cancers and their relationship with lymphatic metastasis.Methods The expres-sion of GPR30,HRG1,HER2 and pHER2 in 72 cases of specimens of invasive ductal breast cancers were examined by immunohis-tochemistry method.Results A moderate correlation between GPR30 and HRG1 was disclosed (r=0.597,P =0.000).There was strong correlation between pHER2 and GPR30 or HRG1(r=0.742,P =0.000;r=0.615,P =0.000).The expression of GPR30 and pHER2 in the lymphatic metastasis group was remarkably higher than in the group without lymphatic metastasis(P <0.05). Conclusion The interaction between GPR30 and HRG1 HER2 signal transduction pathways might be involved in the lymphatic metastasis in breast cancer.Blocking both of GPR30 and HRG1 signaling pathway could be a promising new strategy for breast cancer treatments.

Objective To evaluate the expression of GPR30 and Ki-67 in Non-small cell lung cancer(NSCLC) and the relationship between them.The clinicopathological features of GPR30 in NSCLC were also analyzed.The molecular mechanism that estrogen mediated the proliferation of H1299 by activating GPR30 was further studied.Methods The expression of GPR30 and Ki-67 in 80 cases of specimens of NSCLC after surgery was examined using immunohistochemistry method.After 17-β-estradiol(E2) or G-1 added,H1299 cells were counted and the cell cycle distribution was analyzed by flow cytometry.Finally,the activated ERK1/2 and the expression of cyclin D1 and p16 after G-1 treatment in H1299 cells were examined through western blotting.Results Expressions of GPR30 was more in stage Ⅲ or low differentiation tissues or adenocarcinoma (P＜0.05).A positive correlation between GPR30 and Ki-67 was further disclosed (r=0.502,P=0.000).The proliferation of H1299 cells was promoted and more cells entered S-p hase after E2 or G-1 treatment for 3 days,which could be inhibited after G-15 or U0126 pre-treatment for 2 hours.We further discovered that the activated ERK1/2 and cyclin D1 expression increased after G-1 treatment,which was blocked after G-15 or U0126 pre-treatment for 2 hours.The change of p16 was on the opposite.Conclusion A positive correlation existed between GPR30 and Ki-67.GPR30-EGFR-MAPKs signaling transduction pathway was involved in the estrogen-induced proliferation of NSCLC cells.Blocking GPR30 signaling pathway may be a promising new strategy for NSCLC treatments.

OBJECTIVE:To investigate improvement effect of external administration of water extract from Eriocarpous Glochidion on chronic dermatitis-eczema model mice, and to provide reference for developing new dermatological drug. METHODS:A total of 60 mice were randomly divided into blank group (distilled water), model group (distilled water), compound triamcinolone acetonide acetate group (positive control group, original liquid) , high-concentration, medium-concentration and low-concentration groups of water extract from Eriocarpous Glochidion(2.0,1.0,0.5 g/mL,calculated by crude drug),10 mice in each group. Except for blank group,other groups were given 2,4-dinitrochlorobenzene to induce chronic dermatitis-eczema model. Since the third day of the experiment,two sides of right ears of the mice were given relevant medicine twice at 7:00 and 15:00,15 μL each time,for consecutive 12 d. In the tenth,thirteenth,sixteenth day of the experiment,the difference of thickness of right ears of the mice was calculated(the difference value before experiment),the times of scratching in ear of mice were recorded within 30 min. In sixteenth day of the experiment,ear swelling degree of mice was determined,and thymus index and spleen index in mice were calculated. Optical microscope was used to observe the pathological changes of ear tissues of mice. RESULTS:Compared with blank group,the difference of thickness of right ears,ear swelling degree,spleen index and scratching times were increased significantly in model group(P<0.05 or P<0.01). The epidermis of the ear tissue was thickened,the cell proliferation was obvious,and cavernous edema was found in the epidermis. Compared with model group,other indexes in were decreased significantly,except that the difference value of thickness of right ears in sixteenth day of the experiment,scratching times in ninth and fifteenth day of the experiment were decreased slightly in low-concentration group of water extract from Eriocarpous Glochidion and the thymus index and spleen index in medium-concentration, low-concentration groups of water extract from Eriocarpous Glochidion (P<0.05 or P<0.01). The pathological changes of ear tissue were improved in administration groups to certain extent. CONCLUSIONS:External administration of water extract of Eriocarpous Glochidion has good improvement effect against chronic dermatitis-eczema in mice, which is worthy of further development and investigation.