title: Inhibition of CXCR4 and CXCR7 for reduction of cell proliferation and invasion in human endometrial cancer.
abstract: As one of the most common malignant cancers in female reproductive tract, endometrial cancer accounts for 20-30 % of the most frequent gynecological malignancy, which is originated from endometrial epithelial. The molecular mechanisms for the generation of endometrial cancer are up to now unclear, hindering the development of corresponding therapy. CXCR4 and CXCR7 were receptors of CXCL12 chemokine ligand, which could regulate critical procedures of neoplastic transformation, including proliferation, invasion, and apoptosis of the cells. The messenger RNA (mRNA) and protein expression levels of CXCR4 and CXCR7 in human endometrial adenocarcinoma cancer, as well as in Ishikawa and HEC-1-A cell line, were analyzed by using reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting. In order to explore the biological function of CXCR4 and CXCR7 in endometrial tumor, small interference RNAs of CXCR4 and CXCR7 fragments were designed, synthesized, and transfected into Ishikawa and HEC-1-A by using Lipofectamine2000. The influence of RNA interference (RNAi)-mediated silencing CXCR4 and CXCR7 on the cell proliferation was investigated under CCK-8. The invasion assay was performed transwell, and cell apoptosis was tested by FCM. Higher mRNA and protein expression levels of CXCR4 and CXCR7 were investigated in endometrial adenocarcinomas. The expression levels of CXCR4 and CXCR7 could be inhibited by RNA interference, reducing the cell proliferation, invasion in Ishikawa and HEC-1-A cells. In this study, we also observed that treated with CXCR4 and CXCR7 small interfering RNA (siRNA) arrested cells in S phase. CXCL12/CXCR4 and CXCL12/CXCR7 receptor ligand systems affect the invasion of endometrial carcinoma cell line into Ishikawa and HEC-1-A. CXCR4 and CXCR7 were silenced by RNAi, which can inhibit the invasion of Ishikawa and HEC-1-A cell lines. Hence, CXCR4 and CXCR7 are expected to become two target genes for the treatment of endometrial carcinoma.
authors.affiliation: Department of Gynecology, the Affiliated Hospital of Qingdao University, No.59, Haier Road, Qingdao, 266010, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Long
authors.affiliation: Department of Gynecology, the Affiliated Hospital of Qingdao University, No.59, Haier Road, Qingdao, 266010, People's Republic of China.
authors.forename: Fengyi
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Gynecology, the Affiliated Hospital of Qingdao University, No.59, Haier Road, Qingdao, 266010, People's Republic of China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Gynecology, the Affiliated Hospital of Qingdao University, No.59, Haier Road, Qingdao, 266010, People's Republic of China. huangqwyu@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C501896:ACKR3 protein, human; D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054387:Receptors, CXCR; D019718:Receptors, CXCR4
keywords: CXCL12; CXCR4; CXCR7; Endometrial carcinoma; Gene silencing; HEC-1-A cell line; Ishikawa cell line