RESUMO
BACKGROUND: Telomerase is expressed in most of malignant cells, including lung cancer cells. The success of small interfering RNA (siRNA) in silencing of the telomerase catalytic subunit depends upon carriers ability to efficiently deliver therapeutic agent to cells with minimal toxicity and most biocompatibility. In this study, a potential carrier for efficient delivery was assessed by siRNA encapsulating into Iron MNPs modified with biodegradable polyester nanoparticles consisting of PLGA and PEG. RESULTS: Data analysis shows that the self-assemble diblock copolymers were synthesized, and then the siRNA designed against hTERT catalytic subunit was encapsulated. Also, the rate of telomerase gene expression in equivalent with magnetic copolymers/siRNA was lower than that of free siRNA (P = 0.001). CONCLUSIONS: In conclusion, regarding the enhancing of siRNA stability by magnetic copolymer, the expression of telomerase gene was significantly lower in the cells treated with siRNA-magnetic copolymers than those treated with free siRNA.
Assuntos
Portadores de Fármacos/química , Células Epiteliais/metabolismo , Nanopartículas de Magnetita/química , RNA Interferente Pequeno/genética , Telomerase/genética , Transfecção/métodos , Linhagem Celular Tumoral , Sobrevivência Celular , Células Epiteliais/patologia , Óxido Ferroso-Férrico/química , Expressão Gênica , Inativação Gênica , Humanos , Ácido Láctico/química , Pulmão/metabolismo , Pulmão/patologia , Nanopartículas de Magnetita/ultraestrutura , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , RNA Interferente Pequeno/metabolismo , Telomerase/antagonistas & inibidores , Telomerase/metabolismoRESUMO
BACKGROUND: Herbal compounds such as curcumin which decrease telomerase and gene expression have been considered as beneficial tools for lung cancer treatment. In this article, we compared the effects of pure curcumin and curcumin-loaded NIPAAm-MAA nanoparticles on telomerase and PinX1 gene expression in a lung cancer cell line. MATERIALS AND METHODS: A tetrazolium-based assay was used for determination of cytotoxic effects of curcumin on the Calu-6 lung cancer cell line and telomerase and pinX1 gene expression was measured with real-time PCR. RESULTS: MTT assay showed that Curcumin-loaded NIPAAm-MAA inhibited the growth of the Calu-6 lung cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of curcumin-loaded NIPAAm-MAA increased while expression of the PinX1 gene became elevated. CONCLUSIONS: The results showed that curcumin- loaded- NIPAAm-MAA exerted cytotoxic effects on the Calu-6 cell line through down-regulation of telomerase and stimulation of pinX1 gene expression. NIPPAm-MAA could be good carrier for such kinds of hydrophobic agent.
Assuntos
Resinas Acrílicas/química , Curcumina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Metacrilatos/química , Nanopartículas/química , Telomerase/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Proteínas de Ciclo Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Polímeros/química , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectroscopia de Infravermelho com Transformada de Fourier , Telomerase/genética , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genéticaRESUMO
Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained- release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects.
Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Ácido Láctico/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Ácido Poliglicólico/química , Humanos , Copolímero de Ácido Poliláctico e Ácido PoliglicólicoRESUMO
BACKGROUND: Telomerase has been considered as an attractive molecular target for breast cancer therapy. The main objective of this work is to assess the inhibitory effects of silibinin and curcumin, two herbal substances, on telomerase gene expression in breast cancer cells. MATERIALS AND METHODS: For determination of cell viability tetrazolium-based assays were conducted after 24, 48, and 72 h exposure times and expression of human telomerase reverse transcriptase gene was measured with real-time PCR. RESULTS: Each compound exerted cytotoxic effects on T47D cells and inhibited telomerase gene expression, both in a time-and dose-dependent manner. The mixture of curcumin and silibinin showed relatively more inhibitory effect on growth of T47D cells and hTERT gene expression as compared with either agent alone. CONCLUSIONS: These findings suggest that cell viability along with hTERT gene expression in breast cancer cells could be reduced by curcumin and silibinin.
