title: Growth inhibitory effect of adenovirus-mediated tissue-targeted expression of ribosomal protein L23 on human colorectal carcinoma cells.
abstract: A large body of evidence has established murine double minute 2 (MDM2) as a crucial negative regulator of p53 and the major suppressor of p53 function in tumors with wild-type (wt)-p53. Therefore, by inhibiting MDM2 one may reactivate p53 in tumor cells, leading to their demise. Previous studies revealed that ribosomal protein L23 (RPL23) inhibited MDM2-mediated p53 ubiquitination through direct binding to MDM2, and subsequently induced the p53 level as well as its activity, suggesting that it may be a candidate for use in tumor gene therapy. In the present study, we developed a recombinant adenoviral vector expressing the RPL23 gene under control of the carcinoembryonic antigen (CEA) promoter (rAd/CEA-RPL23), and using an in vitro system with cultured human colorectal carcinoma LoVo cells harboring the wt-p53 gene, we proved that rAd/CEA-RPL23 infection could induce the accumulation of endogenous wt-p53 protein and thus lead to the inhibition of tumor cell growth via inducing cell cycle arrest and apoptosis. In vivo treatment of rAd/CEA-RPL23 also exhibited a significant inhibitory effect on tumor growth in nude mice bearing LoVo xenografts. Furthermore, we showed that rAd/CEA-RPL23 synergized with classic chemotherapeutic agent 5-fluorouracil (5-FU) and enhanced its activity against LoVo cells in vivo and in vitro. Taken together, the data presented here suggest that CEA promoter-targeted exogenous RPL23 expression could be of therapeutic value against human colorectal carcinoma that retains wt-p53.
authors.affiliation: Department of Radiation Oncology, Navy General Hospital, Beijing, P.R. China.
authors.forename: Henghu
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Radiation Oncology, Navy General Hospital, Beijing, P.R. China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Radiation Oncology, Navy General Hospital, Beijing, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Du
authors.affiliation: Department of Radiation Oncology, Navy General Hospital, Beijing, P.R. China.
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Navy General Hospital, Beijing, P.R. China.
authors.forename: Xinhong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiation Medicine and The Ministry of Education, Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, P.R. China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Ren
authors.affiliation: Department of Gastroenterology, General Hospital of the Air Force, PLA, Beijing, P.R. China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Navy General Hospital, Beijing, P.R. China.
authors.forename: Zejun
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Navy General Hospital, Beijing, P.R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Navy General Hospital, Beijing, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Radiation Oncology, Navy General Hospital, Beijing, P.R. China.
authors.forename: Juyi
authors.initials: J
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors; D012269:Ribosomal Proteins / Q000096:biosynthesis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D054875:Ubiquitination / Q000235:genetics
chemical_list: D002272:Carcinoembryonic Antigen; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C032493:ribosomal protein L17; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2