Effects on the STAT3-shRNA in Non-Small-Cell Lung Cancer Therapy: Design, Induction of Apoptosis, and Conjugation with Chitosan-Based Gene Vectors.

STAT3 plays a particularly important role in several cancer-related signal transduction pathways. Silencing STAT3 via RNA interference or small molecule inhibitors induces the apoptosis of tumor cells, thereby inhibiting the growth of the tumors. In this study, short-hairpin RNA sequences targeting the STAT3 genes were designed, synthesized, and then connected to pGPU6/GFP/Neo plasmids as the shRNA-expression vectors. The expression of STAT3-shRNA was analyzed by real-time PCR, western blotting, and cell apoptosis assay to study the growth and apoptosis of the cells. Then, the effect of STAT3 knockdown on the NCI-H1650 cells was studied in a tumor mouse model. The results revealed that, after an in vitro transfection, the proliferation of NCI-H1650 cells was inhibited, and the cells were induced to apoptosis. The mRNA and protein expression levels of STAT3 were downregulated in the STAT3-shRNA group. In vivo, the tumor mass and volume in the STAT3-shRNA group were significantly lower than in the other two groups. Both the in vivo and in vitro results demonstrated a long-period inhibiting effect on NSCLC, especially in vivo, when the tumor inhibition rate could reach 50% in the STAT3-shRNA group, which is an exciting outcome. Moreover, the study of the conjugation of STAT3-shRNA and chitosan-based vectors revealed that they could be combined steadily with good cytocompatibility and transfection efficiency. These results together provide convincing evidence for the application of STAT3-shRNA used in the treatment of non-small lung cancer, which could be a promoting prospect for the development of gene therapy. [ABSTRACT FROM AUTHOR]