Effect of DJ-1 silencing by RNA interference on growth of xenografted human laryngeal squamous cell carcinoma Hep-2 cells in nude mice.
- Author:
Zhisen SHEN
1
;
Hongxia DENG
1
;
Dong YE
1
;
Jian ZHANG
1
;
Shijie QIU
1
;
Qun LI
1
;
Xiang CUI
2
Author Information
1. Department of Otorhinolaryngology, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, China.
2. Ningbo University School of Medicine, Ningbo 315040, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antineoplastic Agents;
pharmacology;
Apoptosis;
drug effects;
genetics;
Carcinoma, Squamous Cell;
chemistry;
genetics;
physiopathology;
Caspase 3;
analysis;
drug effects;
Cell Line, Tumor;
chemistry;
drug effects;
physiology;
transplantation;
Cell Proliferation;
drug effects;
Down-Regulation;
Gene Expression Regulation;
drug effects;
genetics;
physiology;
Head and Neck Neoplasms;
chemistry;
genetics;
physiopathology;
Heterografts;
drug effects;
physiology;
Humans;
Inhibitor of Apoptosis Proteins;
analysis;
drug effects;
Ki-67 Antigen;
analysis;
drug effects;
Laryngeal Neoplasms;
chemistry;
genetics;
physiopathology;
Mice, Nude;
PTEN Phosphohydrolase;
analysis;
drug effects;
Phosphatidylinositol 3-Kinases;
drug effects;
Protein Deglycase DJ-1;
pharmacology;
Proto-Oncogene Proteins c-akt;
drug effects;
RNA Interference;
physiology;
RNA, Messenger;
pharmacology;
RNA, Small Interfering;
physiology;
Signal Transduction;
drug effects;
genetics;
physiology
- From:
Journal of Zhejiang University. Medical sciences
2016;45(4):349-355
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the effect of silencing DJ-1 on xenografted human laryngeal squamous cell carcinoma (LSCC) Hep-2 cells in nude mice.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 (=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.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, all<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 (all<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 (all<0.05), while PTEN mRNA and protein content increased (all<0.05).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.
