EFFECT OF TIGAR KNOCKOUT ON THE APOPTOSIS OF A549 CELLS AND EXPRESSION OF EPITHELIAL MESENCHYMAL MARKERS IN DOX-RESISTANT NON-SMALL CELL LUNG CANCER

Lin Chu^{1, #, *}, Dezhan Li^{2, #}, Xuefen Fei³, Wenming Feng⁴, Hongxing Zhao⁴

¹Department of Thoracic surgery, Affiliated RenHe Hospital of China Three Gorges University, Yichang, Hubei, 443000, PR China - 

²Department of Anesthesiology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei, 434020, P R China - ³Department of Respiration, The Linghu People’s Hospital of Nanxun District  Huzhou, Huzhou 313018, Zhejiang, PR China - ⁴Department of Surgery, The First People’s Hospital of Huzhou (The First Affiliated Hospital of Huzhou  University), Huzhou 313000, Zhejiang, PR China

Objective: To investigate the effect of TIGAR knockout on the apoptosis of A549 cells and expression of epitheli-al/mesenchymal markers in doxorubicin (DOX)-resistant non-small cell lung cancer (NSCLC). 

Methods: A DOX-resistant A549 cell line (A549/DOX) was established in this study, and the gene was knocked out through TIGAR-targeted siRNA reverse transfection. The TIGAR protein, cell viability, colony survival, ROS, NADPH and expression levels of apoptosis-related markers and epitheli-al/mesenchymal markers of the control group and siRNA transfection group were compared. 

Results: After DOX treatment, the cell viability of A549/DOX cell line was significantly higher than that of the original A549 cell line (P<0.05). The TIGAR protein, cell viability, colony survival, levels of NADPH, Bcl-2, PARP and vimentin in the siTIGAR transfection group were significantly lower than those in the control group (P<0.05). The levels of ROS, Bax, Caspase-3, Caspase-9, PARP degradation products and E-caderin in the siTIGAR transfection group were significantly higher than those in the control group (P<0.05). 

Conclusion: TIGAR knockout can inhibit the EMT of DOX-resistant NSCLC and be used as a potential therapeutic target for patients with chemotherapy resistance.