RESUMO
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.
Assuntos
Animais , Humanos , Antineoplásicos , Farmacologia , Apoptose , Genética , Carcinoma de Células Escamosas , Química , Genética , Caspase 3 , Linhagem Celular Tumoral , Química , Fisiologia , Transplante , Proliferação de Células , Regulação para Baixo , Regulação da Expressão Gênica , Genética , Fisiologia , Neoplasias de Cabeça e Pescoço , Química , Genética , Xenoenxertos , Fisiologia , Proteínas Inibidoras de Apoptose , Antígeno Ki-67 , Neoplasias Laríngeas , Química , Genética , Camundongos Nus , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases , Proteína Desglicase DJ-1 , Farmacologia , Proteínas Proto-Oncogênicas c-akt , Interferência de RNA , Fisiologia , RNA Mensageiro , Farmacologia , RNA Interferente Pequeno , Fisiologia , Transdução de Sinais , Genética , FisiologiaRESUMO
After the rats with hyperlipidemia were orally treated with the compound of Silymarin and Fenofibrate for 3 weeks, the blood levels of TC, LDL-c, VLDL-c in serum were significantly decreased. Especially, the concentration of HDL-c was greatly increased. The contents of TC and TG in the rat' s liver were also significantly decreased. It was also found that the effects of the compound of Silymarin and Fenofibrate on the level lipoprotein and TC or TG in liver were more significantly that of Silymarin or Fenofibrate alone