ABSTRACT
BACKGROUND: Nanoparticles have an enormous potential for development in biomedical applications, such as gene or drug delivery. In our study, we examined the efficacy of p53 gene therapy in human breast carcinoma (MCF-7) cells using silica nanoparticles (SiNPs) supplemented with transferrin. METHODS: MCF-7 cells were exposed to transferrin-SiNPs-p53 in vitro, and the growth inhibition rate, expression of p53 and bax, and induction of apoptosis were measured 48 h later. RESULTS: Treatment of MCF-7 cells with transferrin-SiNPs-p53 resulted in 60.7 % growth inhibition. Wild-type p53 expression and an increase in bax expression were observed following transfection with transferrin-SiNPs-p53, and 20.5 % of the treated MCF-7 cells were apoptotic. In vivo, the MCF-7 tumor transplanted into nude mice grew to 5-6 mm in diameter. Following growth of the tumor to this size, transferrin-SiNPs-p53 was locally applied to the peripheral tumor (day 0) and then applied once every 5 days for a total of six times. During the administration period, tumor growth did not occur, and the mean tumor volume on the last day of administration (day 25) was 10.0 % of that in the saline control group. CONCLUSION: These results suggest that p53 gene therapy via transferrin-modified silica nanoparticles is an effective strategy for treatment of breast carcinoma.
Subject(s)
Apoptosis/genetics , Breast Neoplasms/therapy , Carcinoma/therapy , Cell Proliferation/genetics , Genes, p53 , Genetic Therapy/methods , Nanoparticles , Silicon Dioxide , Transferrin , bcl-2-Associated X Protein/metabolism , Animals , Blotting, Western , Breast Neoplasms/genetics , Carcinoma/genetics , Female , Humans , In Situ Nick-End Labeling , In Vitro Techniques , MCF-7 Cells , Mice , Mice, Nude , Neoplasm Transplantation , Receptors, Transferrin/metabolism , Transfection , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
In our previous investigations, urine of female mice contained specific compounds, namely isocroctylhydrazine, 4-methyl-2-heptanone, and azulene during proestrus, whereas during estrus it contained 1-H-cyclopop.e.azulene, caryophyllene, and copanene. Furthermore, 1-iodo-2 methyl undecane (1I2MU), present during both proestrus and estrus, was regarded as a putative estrus-specific chemo-signal. The primary objective of the present study was to determine the estrogen-dependency of the above-mentioned compounds, including 1I2MU. Furthermore, the effect of these compounds on pre-mating behavior, e.g., sniffing, licking, and grooming, were recorded to determine their role as sex pheromones. Based on gas chromatography linked mass spectrometry (GC-MS) of urine samples, profiles in oophorectomized female mice had 14 major peaks. Furthermore, neither 1I2MU (nor other estrus-specific compounds) were detected in the urine of these mice, although they were detected in urine of proestrus and estrus mice. In addition, 1I2MU was not detected in urine of prepubertal mice. It was noteworthy that both 1I2MU and 4-methyl-2-heptanone reappeared in estrogen-treated females. Based on pre-mating behavioral analysis, 1I2MU was the compound most preferred by males. In conclusion, production of 1I2MU was estrogen-dependent in females, and it enhanced reproductive activities in males.
