title: Efficient inhibition of human colorectal carcinoma growth by RNA interference targeting polo-like kinase 1 in vitro and in vivo.
abstract: Polo-like kinase 1 (PLK1) showing a high expression in various kinds of tumors is considered a candidate target for cancer therapy. The aim of our study was to explore the effects of silencing PLK1 gene on human colorectal carcinoma cell line HCT-116 in vitro and in vivo. In vitro, the plasmids generating short hairpin RNA (shRNA)-targeting PLK1 were transfected into HCT-116 by using FugeneHD reagent, and the silencing potency was measured by RT-PCR, western blot, flow cytometry, and Caspase-Glo 3/7 assay, respectively. In vivo, the growth inhibition capacity of PLK1-shRNA on HCT-116 xenograft was measured in nude mice. Then, the silencing effect of PLK1 was analyzed by RT-PCR, western blot, and immunohistochemistry, respectively. Apoptosis, angiogenesis, and proliferation in tumor tissues were measured by TUNEL, CD31, and PCNA stain, respectively. The RNA interference targeting PLK1 significantly decreased the expression of PLK1 in vitro. More importantly, anti-PLK1 treatment in HCT-116 xenograft decreased tumor weight by 81.58% compared with the control group (p<0.001), accompanied with decreased PLK1 mRNA and protein expression, increased cell apoptosis, and reduced angiogenesis and proliferation (p<0.001). Our study showed that knockdown of PLK1 by shRNA might be the potential therapeutic approach against human colorectal carcinoma.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital and West China Medical School, Sichuan University, Ke-yuan Road 4, No. 1 Gao-peng Street, Chengdu, Sichuan, The People's Republic of China .
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Xu
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Sheng-Yong
authors.initials: SY
authors.lastname: Liu
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Tian
authors.forename: Lei
authors.initials: L
authors.lastname: Dai
authors.forename: Qian
authors.initials: Q
authors.lastname: Xie
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015536:Down-Regulation; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1