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

• 作者: ZHANG Wangwang ZHANG Yan JIANG Zhiwen SUN Le WANG Litong GU Zhiyang LI Wenya GUO Lili CHEN Xiaotong ZHANG Haibin HAN Baoqin CHANG Jing
• 来源期刊: 中国海洋大学学报（自然科学英文版）
• 年，卷（期）: 2021,（5）
• 所属期刊栏目: Marine and Atmospheric Sciences
• 页码范围: 1097-1108
• 页数: 12页
• 语种: 英文

摘要

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 cytocompati-bility 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.