Effects of GRIM-19 on chemotherapeutic sensitivity of cisplatin-resistant human lung cancer cell A549/DDP and the expressions of related genes

Objective: To investigate the effects of gene-associated with retinoid-interferon-induced mortality 19 (GRIM-19) on chemotherapeutic sensitivity of cisplatin (DDP)-resistant human lung caner cell A549/DDP and the expressions of related genes. Methods: The recombinant plasmid PIRES-Puro2-GRIM-19-Myc and the empty vector PIRES-Puro2-Myc were transfected into A549/DDP cells by liposome transfection reagent, respectively. The expression levels of GRIM-19 protein in the A459 parental cells, A459/DDP cells, A549/DDP cells transfected with GRIM-19 gene and A549/DDP cells transfected with an empty vector were detected by Western blotting. The changes of chemotherapeutic sensitivities to multi-drugs in A549/DDP cells stably transfected with GRIM-19 gene were detected by MTT assay. The expression levels of GRIM-19, signal transducers and activators of transcription 3 (STAT3), vascular endothelial growth factor (VEGF) and P-glycoprotein (P-gp) mRNAs in the A549/DDP cells stably transfected with GRIM-19 gene were examined by real-time fluorescence quantitative-PCR (RFQ-PCR). Results: The Western blotting result showed that the expression level of GRIM-19 protein was increased in the A549/DDP cells after transfection with GRIM-19 gene. The resistance index of A549/DDP cells was 16.86±1.32 folds higher than that of the A549 parental cells. The resistance index of the A549/DDP cells after transfection with GRIM-19 gene was decreased by 3.70±0.91 folds as compared with that of the A549/DDP cells transfected with an empty vector. The expression levels of STAT3, VEGF and P-gp mRNAs in the A549/DDP cells transfected with GRIM-19 gene were decreased. Conclusion: GRIM-19 can increase the chemotherapeutic sensitivity of A549/DDP cells. This effect may be associated with the down-regulations of STAT3, VEGF and P-gp. GRIM-19 may become a potential therapeutic agent to reverse drug-resistance in A549/DDP cells. DOI:10.3781/j.issn.1000-7431.2012.02.003