title: Adenovirus-mediated RhoA shRNA suppresses growth of esophageal squamous cell carcinoma cells in vitro and in vivo.
abstract: Over-expression of RhoA in esophageal squamous cell carcinoma (ESCC) indicates a poor prognosis and is correlated with the tumor-node-metastasis (TNM) clinical classification. However, until now RhoA function in the ESCC progression remains to be established. We employed adenovirus-mediated small hairpin RNA (shRNA) against human RhoA (Ad-sh-RhoA) to efficiently silence target gene expression in RhoA-expressing Eca-109 ESCC cells at both protein and mRNA levels. Consequently, Ad-sh-RhoA reduced the proliferation and migration of Eca-109 cells assayed by MTT assay and cell wound healing, respectively. Moreover, Ad-sh-RhoA increased cell apoptosis and inhibited the cell cycle G1-S-phase progression of Eca-109 cells assessed by flow cytometry. Finally, in a nude mouse model, intratumoral injections of adenovirus-delivered RhoA shRNA every 3 days for 20 days significantly inhibited the growth and angiogenesis of xenografted Eca-109 tumors. In summary, these data indicate that RhoA may be a key molecule in ESCC cells, and thus, specific inhibition of the Rho signaling pathway with adenovirus-delivered shRNA represents a promising approach for the treatment of aggressive ESCC.
authors.affiliation: Department of Oncology, Xijing Hospital, The Fourth Military Medical University, 710032 Xi'an, People's Republic of China.
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Ma
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
authors.forename: Yuanxiong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
authors.forename: Wenchao
authors.initials: W
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae; D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002469:Cell Separation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020742:rhoA GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein