title: Down-regulation of HPV18 E6, E7, or VEGF expression attenuates malignant biological behavior of human cervical cancer cells.
abstract: To investigate the effect of down-regulation of VEGF (vascular endothelial growth factor) and HPV18 E6/E7 by hairpin RNA (shRNA) on cell proliferation, apoptosis, migration, invasion, and adhesion abilities of cervical carcinoma cells, recombinant plasmids including pS-E6 shRNA, pS-E7 shRNA, and pS-VEGF shRNA were constructed and transfected into HeLa cells. The levels of E6 mRNA, E7 mRNA, or VEGF mRNA were significantly reduced after transfection of pS-E6 shRNA (76.0%), pS-E7 shRNA (74.4%), and pS-VEGF shRNA (46.7%). VEGF expression was down-regulated by pS-E6 shRNA (55.1%) and pS-E7 shRNA (46.6%). The apoptosis of HeLa cells was increased, and the proliferation, invasion, and adhesion abilities were decreased significantly. For in vivo study, cancer cells that stably expressed the plasmids were cultured. Cells were transplanted subcutaneously into nude mice to establish xenograft tumor model. Finally, expression of E6 shRNA, E7 shRNA, and VEGF shRNA in cancer cells led to inhibition of the growth of xenograft. Hence, RNA interference could effectively suppress the expression of HPV18 E6/E7 and VEGF in human cervical cancer cells. This suppression attenuates malignant biological behavior of human cervical cancer cells. RNA interference of HPV E6/E7 or VEGF expression implies an effective anti-cervical cancer strategy.
authors.affiliation: Department of Pathology, Nantong University School of Medicine, 226001 Nantong, China. bl1@ntu.edu.cn
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wu
authors.forename: Peigen
authors.initials: P
authors.lastname: Liu
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
authors.forename: Guilan
authors.initials: G
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Qin
authors.forename: Jiaming
authors.initials: J
authors.lastname: Zhou
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A