title: [Effect of DJ-1 silencing by RNA interference on growth of xenografted human laryngeal squamous cell carcinoma Hep-2 cells in nude mice].
abstract: Objective:To investigate the effect of silencing DJ-1 on xenografted human laryngeal squamous cell carcinoma (LSCC) Hep-2 cells in nude mice.Methods:Xenograft model of human LSCC was established by subcutaneous transplantation of Hep-2 cells in 24 nude mice. The LSCC-bearing nude mice were randomly divided into 3 groups (n=8 in each):DJ-1 siRNA low dose group and DJ-1 siRNA high dose group were injected in tumors with 20 μg of DJ-1 siRNA or 40 μg of DJ-1 siRNA in 50 μL, respectively; control group was injected with 5% glucose solution in 50 μL, twice a week for 3 weeks. The weight and size of tumors were measured before injection. The animals were sacrificed 48 h after the final treatment, and the tumors were harvested and weighed. The apoptosis and proliferation of tumor cells were determined; the expressions of Caspase-3 and Ki-67 in tumor specimens were detected with immunohistochemistry. The expression of DJ-1, PTEN, survivin mRNA and protein in tumor tissues were detected by RT-PCR and Western blotting, respectively.Results:Tumor weight in low dose group[(0.66±0.15)g] and high dose group[(0.48±0.11)g] were significantly lower than that in control group[(0.83±0.16)g, allP<0.05]. The inhibition rates of low dose group and high dose group were (20.48±0.18)% and (42.16±0.13)%, respectively. Immunohistochemistry showed that the expression of Caspase-3 was increased and Ki-67 was reduced in tumor specimens, compared with the control group (allP<0.05). RT-PCR and Western blot results showed that in low dose group and high dose group the mRNA and protein expression of DJ-1 and survivin significantly decreased (allP<0.05), while PTEN mRNA and protein content increased (allP<0.05).Conclusion:High dose DJ-1 siRNA can inhibit the tumor growth in human LSCC xenograft nude mouse model, which indicates that down-regulating DJ-1 and survivin, and up-regulating PTEN expression may lead to blockage of PI3K-PKB/Akt signaling pathway and promoting tumor cell apoptosis.
authors.affiliation: Department of Otorhinolaryngology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China.
authors.forename: Zhisen
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Otorhinolaryngology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Otorhinolaryngology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ye
authors.affiliation: Department of Otorhinolaryngology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Department of Otorhinolaryngology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.affiliation: Ningbo University School of Medicine, Ningbo 315040, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000503:physiopathology*; D053148:Caspase 3 / Q000032:analysis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology / Q000637:transplantation; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000503:physiopathology*; D064593:Heterografts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis / Q000187:drug effects; D019394:Ki-67 Antigen / Q000032:analysis / Q000187:drug effects; D007822:Laryngeal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000503:physiopathology*; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D000071617:Protein Deglycase DJ-1 / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D034622:RNA Interference / Q000502:physiology*; D012333:RNA, Messenger / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000071617:Protein Deglycase DJ-1; D051059:PTEN Phosphohydrolase; D053148:Caspase 3