RESUMO
The current study aimed to evaluate the role and underlying mechanism of cyclic adenosine phosphate (cAMP) on the functional recovery of spinal cord injury (SCI). Basso, Beattie and Bresnahan (BBB) scoring and inclined plane test indicated that cAMP treatment improved the functional recovery of SCI rats. Real time PCR and western blot analysis showed the mRNA and protein levels of IRE1, PERK, and ATF6 were increased in the SCI rats than those of sham control. However, higher levels of IRE1, PERK, and ATF6 were indicated after cAMP treatment. Meanwhile, more apoptotic cells were observed in the SCI rats, as evidenced by TUNEL staining and increased expression of GRP78, CHOP, and caspase12. In contrast, the expression of GRP78, CHOP, and caspase12 was decreased in SCI rats after cAMP treatment. In summary, we showed novel data that cAMP reduced cell apoptosis and functional recover after SCI mainly via activating UPR.
Assuntos
AMP Cíclico/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Fator 6 Ativador da Transcrição/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 12/metabolismo , AMP Cíclico/farmacocinética , Proteínas de Choque Térmico/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Atividade Motora/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia , Vértebras Torácicas/patologia , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismoRESUMO
IGF-1R is expressed abnormally in osteosarcoma (OS) and could participate in its progression. In this study, we aimed to explore the effect of the IGF-1R inhibitor PQ401 as a treatment for OS. The relative expression of IGF-1R in OS patient tumors and the U2OS cell line were determined by qRT-PCR and by accessing information in a public database. Inhibition of cell proliferation by PQ401 was determined by MTT assay. Cell migration under low concentration treatment of PQ401 was carried out by transwell and wound healing assays. PQ401 induction of OS cell apoptosis was investigated by flow cytometry. Tumorigenesis under PQ401 treatment was evaluated by a colony formation assay. Finally, downstream blockage of the IGF-1R pathway was verified by western blotting. Our results show that the expression of IGF-1R was remarkably higher in OS cells, particularly in U2OS, than in other cancer-type cell lines. The inhibition of the IGF-1R pathway by PQ401 exhibited significant anticancer activity in the U2OS cell line in not only proliferation but also migration and colony formation. In addition, PQ401 is a strong inducer of OS cell apoptosis. Furthermore, western blotting was used to demonstrate that the IGF-1R related downstream pathway, including total ERK1/2, was significantly inhibited by PQ401. Thus, IGF-1R inhibition may represent a novel treatment for OS.
