Abstrakt

Gd3+-DTPA-bis (N-methylamine)-Dendrimer significantly alters Bax/Bcl2 gene expression levels in MCF-7 cancer cells

Bahar Javani, Sara Fattah, Mostafa Saffari, Mehdi Shafiee Ardestani

Nanoparticles and their engineering are widely used in diagnosis, drug delivery and therapeutic agents, and have provided a new perspective to clinical diagnostic methods, advanced imaging and treatment of cancer. In recent years, investigating pharmacogenetics and corona protein effects of nanoparticles in biological applications has been seriously considered. Since apoptosis is a major mechanism of tumor suppression in the body so investigating the effects of drugs such as nanoparticles through inducing apoptosis pathway can be a proper therapeutic strategy for a variety of cancers. In this study, the mechanism of apoptosis induced by Gd³⁺-DTPA-bis (N-methylamine)-Dendrimer was investigated compared to Omniscan as a contrast agent on epithelial cell line of MCF-7 through investigating the expression of Bcl-2, Bax, caspase 3 and 9, and GAPDH in mitochondrial pathway. In order to demonstrate the effect of drugs on the genome, a quantitative method was used to estimate PCR products called Real-time PCR. Also the interaction of plasma proteins was investigated by Gd³⁺-DTPAbis (N-methylamine)-Dendrimer compared with Omniscan using SDS-PAGE technique to determine the fate of nanoparticles. Conducted study showed acceptable therapeutic effect of Dendrimer Gd³⁺-DTPAbis (N-methylamine)-compared with Omniscan in vitro of model of breast cancer compared to normal cells. Therefore, the use of the nanoparticles can be effective on increasing expression of some suppressing metastasis genes and pro-apoptotic. No significant result of the effect on caspases was observed. But a significant effect was observed on Bax and Bcl-2. (p<0/05) Also in this study, corona protein was investigated and the protein with weight less than 70 kDa was observed around A nanoparticle that seems albumin protein with a molecular weight of 67 kDa.