RESUMO
Ameloblastin (AMBN), the most abundant non-amelogenin enamel matrix protein, plays a role in ameloblast differentiation. Previously, we found that AMBN promoted osteogenic differentiation via the interaction between CD63 and integrin ß1, leading to the inactivation of Src; however, how AMBN affects the malignant behavior of osteosarcoma is still unclear. Osteosarcoma affects the bone and is associated with poor prognosis because of the high rate of pulmonary metastases and drug resistance. Here we demonstrated that stable overexpression of AMBN induced apoptosis and suppressed colony formation and cell migration via the inactivation of Src-Stat3 pathway in human osteosarcoma cells. Moreover, AMBN induced chemosensitivity to doxorubicin. Thus, AMBN induced a tumor suppressive phenotype and chemosensitivity to doxorubicin via the AMBN-Src-Stat3 axis in osteosarcoma. Indeed, immunohistochemical expression of AMBN was significantly correlated with better outcome of osteosarcoma patients. Our findings suggest that AMBN can be a new prognostic marker and therapeutic target for osteosarcoma combined with conventional doxorubicin treatment.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Proteínas do Esmalte Dentário/metabolismo , Doxorrubicina/farmacologia , Proteína Oncogênica pp60(v-src)/antagonistas & inibidores , Osteossarcoma/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Camundongos Nus , Modelos Biológicos , Transplante de Neoplasias , Osteossarcoma/patologia , Resultado do TratamentoRESUMO
We evaluated the efficacy of a magnetic liposomal delivery system of transforming growth factor (TGF)-beta(1) in the treatment of articular cartilage defects in a rabbit model. Articular cartilage defects were created in the patellar groove of rabbits, and a permanent magnet or a nonmagnetic alloy was implanted in the defect site. Magnetic liposomal drugs, prepared by the conventional film method and sonication, were injected into the defect site 1 week after surgery. First, the efficacy of the magnetic liposomal delivery system was evaluated by using a model compound fluorescence-labeled dextran 40,000 (FD-40). Then, the therapeutic efficiency of magnetic liposomal TGF-beta(1) was evaluated by cartilage histological scoring at 4, 8, and 12 weeks after surgery. The injected magnetic liposomal FD-40 accumulated at the target site where a permanent magnet had been implanted. The histological score showed that the injection of magnetic liposomal TGF-beta(1) under magnetic force was significantly effective in the repair of the defect site over 12 weeks after surgery. Injection of TGF-beta(1) into the cartilage defect was effective as a magnetic liposomal preparation under magnetic force, resulting in acceleration of the cartilage repair, probably because of the desirable accumulation of TGF-beta(1) at the target site.
