The Study Of Sh-miR-34a Entrapped By Dendrimer Polymer For Malignant Melanoma Therapy

Melanoma(malignant melanoma, MM) is a malignant tumor caused by the melanocytes. Its shift occurred early which resulted in a high mortality rate. Currently, the incidence of MM in China is increased. Patients do not get appropriate treatment due to the lack of knowledge about MM. Traditional methods of clinical treatment of MM include surgery and chemotherapy. Using new technology to overcome strong side effects and overcome poor patient compliance during the traditional treatment are the focus of current research. With the development of tumor pathogenesis and genetic engineering techniques, gene therapy is becoming popular in the field of treatment of MM.Gene therapy is using new technologies to transfer exogenous gene into a living organism for the treatment of diseases caused by genetic defects and abnormality. Dendrimer polymer(PAMAM) and sh-miR-34 a which can express miR-34 a were employed as a non-viral carrier material and gene drug for the treatment of MM in the paper. PAMAM / sh-miR-34 a nanocomplex was constructed by electrostatic principles and characterized. The particle size and potential of PAMAM / sh-miR-34 a at N / P = 20 were 180 nm and 30 mV. Agarose gel electrophoresis showed that sh-miR-34 a can be effectively wrapped by PAMAM in N / P = 5. In addition, anti-tumor effect of PAMAM / sh-miR-34 a nanocomplex was studied in vitro. A375 cell uptake experiments found that uptake of PAMAM / sh-miR-34 a nanocomplex was 80%. Results of CCK8 found that the proliferation of A375 cells can be effectively inhibited by PAMAM / sh-miR-34 a nanocomplex in vitro and its survival rate was only 61.2 ± 2.5%. Cell migration and invasion assay showed that migration and invasion of A375 cell were inhibited by PAMAM / sh-miR-34 a nanocomplex. Finally, the anti-tumor effect in vivo of PAMAM / sh-miR-34 a was investigated. A375 xenograft tumor model was constructed utilizing subcutaneous injection. The result showed that the growth of A375 tumor was inhibited by PAMAM / sh-miR-34 a. Tumor volume of the PAMAM / sh-miR-34 a group was only 74.8% of the control group and the tumor mass of PAMAM / sh-mi R-34 a group was only 66.9% of the control group.In this paper, PAMAM / sh-miR-34 a drug delivery system was successfully constructed. Its potential, particle size, wrapping capability and anti-proliferative effect in vitro were studied. This mechanism of the inhibition of A375 cells is the inhibition of phosphorylation of protein kinase(extracellular regulated protein kinases) ERK1 and ERK2 and phosphorylated AKT kinase caused by the expression of miR-34 a. In vivo experiments also showed the effective anti-tumor effect by sh-miR-34 a on tumor-bearing nude mice.