RESUMO
Here, we investigated the effects of dual delivery of IGF-1R siRNA and doxorubicin by chitosan nanoparticles on viability of A549 lung cancer cells line by utilization of MTT and qRT-PCR. Furthermore apoptosis and migration of treated cells were assessed by Annexin-PI and wound healing assays, respectively. The chitosan nanoparticles had about 176 nm size with zeta potential and polydispersive index about 11 mV and 0.3, respectively. The IGF-1R siRNA had synergistic effect on DOX-induced cytotoxicity and apoptosis in tumour cells. In addition, siRNA/DOX-loaded chitosan nanoparticles could significantly decrease migration and expressions of mmp9, VEGF and STAT3 in A549 cells.
Assuntos
Quitosana/química , Doxorrubicina/química , Neoplasias Pulmonares/patologia , Nanopartículas/química , RNA Interferente Pequeno/química , Receptor IGF Tipo 1/deficiência , Receptor IGF Tipo 1/genética , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/genética , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Metaloproteinase 9 da Matriz/genética , Invasividade Neoplásica , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/genética , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
The type 1 IGF receptor (IGF1R) and mesenchymal-epithelial transition (MET) are hetrodimeric and transmembrane receptor tyrosine kinases, which are frequently overexpressed by several tumor types, including colorectal cancer (CRC). These receptors bind to their specific ligands, insulin growth factors (IGFs) and hepatocyte growth factor (HGF), respectively, and promote signaling cascades which mediates many functions such as proliferation and protection against apoptosis, cell scattering, tumor cell motility, invasion and metastasis. In patients with metastatic colorectal cancer (mCRC), IGF1R and c-met expression confer resistance to cetuximab (monoclonal antibodies against EGFR). Therefore, the c-met and IGF1R are now an attractive novel target for anticancer therapy. In this review, we will describe correlation between two receptors and their activation effects in tumor cells, and finally introduce useful and available strategies for their targeting.
