Localized RNA interference therapy to eliminate residual lung cancer after incomplete microwave ablation

Thoracic Cancer

卷:10

Lin Xie¹  Weijun Fan¹  Han Qi¹  Lujun Shen¹  Fei Cao¹  Shuanggang Chen¹  Chao Wan²  Ze Song³ 

[1] Department of Minimally Invasive Interventional Center Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou China;

[2] Department of Oncology Shandong Provincial Hospital Affiliated to Shandong University Jinan China;

[3] Department of Oncology The Seventh Affiliated Hospital, Sun Yat‐sen University Shenzhen China;

关键词: EGFR;    gene therapy;    intra‐tumor injection;    lung cancer;    microwave ablation;   

DOI  :  10.1111/1759-7714.13079

来源: DOAJ

【 摘 要 】

Background This study evaluated the safety and efficacy of localized injection of polyethylene glycol (PEG)‐hyperbranched polyethyleneimine (PEI)‐EGFR‐small interfering RNA (siRNA) nanocomposites as a treatment for residual lung cancer after incomplete microwave ablation (MWA). Methods Human lung cancer cell lines with high and low EGFR expression were selected for the study. The effects of PEG‐PEI‐EGFR‐siRNA nanocomposite transfection on the proliferation, migration, and apoptosis of lung cancer cells were verified. Sixteen healthy ICR mice were injected into the lung to test the biological safety of the nanocomposites. In addition, 24 subcutaneous xenograft BALB/C nude mice with high EGFR expression were separated into four groups and then treated with an intratumoral injection of PEG‐PEI‐EGFR‐siRNA, PEG‐PEI‐normal control (NC)‐siRNA, PEG‐PEI‐EGFR‐siRNA after MWA, or PEG‐PEI‐NC‐siRNA after MWA. Tumor growth, pathological changes, and EGFR expression in each group were observed. Results PEG‐PEI‐EGFR‐siRNA nanocomposites were transfected to HCC 827 cells showing high EGFR expression and to H23 cells showing low EGFR expression. In HCC827 cells, downregulation of EGFR gene expression reduced cell proliferation, invasion, and migration, whereas cell apoptosis increased. In contrast, in H23 cells, no significant differences in those parameters were detected. No acute toxicity occurred in the ICR mice during the biosafety test. Localized injection of PEG‐PEI‐EGFR‐siRNA nanocomposites significantly inhibited the growth of human lung xenografts in mice and the growth of residual tumors after MWA. Conclusion PEG‐PEI‐EGFR‐siRNA nanocomposites may be a supplemental therapy strategy to treat residual lung cancer after incomplete MWA.

【 授权许可】

Unknown