RESUMO
Glioblastoma (GBM) is one of the most lethal tumor of all human cancers. Due to its poor response to chemotherapy and radiotherapy as well as its high rate of recurrence after treatment, the treatment is still undesired. The identification of potential related genes and bio-markers in the development of GBM could provide some new targets for the treatment of GBM. Our purpose in this study was to evaluate the mission of COL8A2 in GBM. Combined with TCGA, Oncomine databases, CGGA, GEPIA website and qRT-PCR analyses, we found that COL8A2 was up-regulated both in GBM tissues and cells compared to the controls. Moreover, the high COL8A2 expression was associated with the shorter overall survival of patients with GBM. The expression of COL8A2 was also positively correlated with metastasis-associated genes including vimentin, snail, slug, MMP2 and MMP7 according to GEPIA website. Knockdown of COL8A2 could suppress the cell proliferation, cell migration and invasion, whereas the overexpression of COL8A2 significantly expedited these processes. What's more, the outcome of western blot analysis manifested that COL8A2 could induced the expression of vimentin, snail, slug, MMP2 and MMP7. Taken together, COL8A2 activated cell proliferation, cell migration and invasion via raising the relative expression of EMT-related proteins in GBM. Therefore, our investigation suggests the oncogenic role of COL8A2 in GBM and provides a potential application of COL8A2 for GBM therapy.
Assuntos
Membrana Basal/metabolismo , Neoplasias Encefálicas/metabolismo , Colágeno Tipo VIII/metabolismo , Endotélio Corneano/metabolismo , Glioblastoma/metabolismo , Membrana Basal/patologia , Neoplasias Encefálicas/patologia , Endotélio Corneano/patologia , Transição Epitelial-Mesenquimal , Glioblastoma/patologia , Humanos , TransfecçãoRESUMO
The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the bloodbraintumor barrier. In the present study, cyclic ArginineGlycineAspartic acidDTyrosineLysine [c(RGDyK)], that has a high binding affinity to integrin αvß3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acidpolyethylene glycol (DTXPLAPEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the ArginineGlycineAspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTXPLAPEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas nontargeted micelles showed limited transport ability. Furthermore, RGDlinked micelles showed marked antiglioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligandmediated drug delivery may improve the efficacy of brain cancer chemotherapy.