title: Silencing of CXCR4 by RNA interference inhibits cell growth and metastasis             in human renal cancer cells.
abstract: Renal cell carcinoma (RCC) is the third most common genitourinary malignancy,             accounting for 3% of cancer in adults. The mortality and morbidity of RCC is strongly             associated with its high propensity to metastasize to specific organs. This may             be attributed to the fact that the CXCR4 G protein-coupled receptor (GPCR) on             RCC cells mediates chemoattraction toward stromal-derived factor 1 (SDF-1) secreted             by target organs. RNA interference (RNAi), which has been proven to be a powerful             tool for suppressing gene expression, may lead to novel strategies for treating             RCC. Our previous experiments confirmed that RCC A-498 cells overexpressing CXCR4             are associated with increased invasiveness. In this study, we constructed recombinant             CXCR4-RNAi plasmids and transfected them into A-498 cells in vitro. Reverse transcription             polymerase chain reaction (RT-PCR) and western blotting revealed that CXCR4 was             downregulated in transfected cells compared with control cells. Our results from             MTT and transwell migration assays indicated that specific downregulation of CXCR4             inhibited cell growth, invasiveness and migration. Flow cytometric analysis indicated             that silencing of CXCR4 in A-498 cells by RNA interference induced cell apoptosis             in RCC in vitro. Thus, siRNA targeting of CXCR4 can effectively inhibit the growth             and metastasis of RCC cells and may be a promising innovative anticancer therapy.
authors.affiliation: Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Linhui
authors.initials: L
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Gao
authors.forename: Tie
authors.initials: T
authors.lastname: Zhou
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Wu
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4