Breast cancer metastasis suppressor 1 gene enhances the sensitivity of osteosarcoma cells to paclitaxel

Abstract

Objective To investigate the mechanism of overexpression of breast cancer metastasis suppressor 1 (BRMS1) gene on the sensitivity of paclitaxel in osteosarcoma. Methods Human osteosarcoma MG-63 cells were divided into blank group, pcDNA3.1-BRMS1 group, paclitaxel group and pcDNA3.1-BRMS1 + paclitaxel group. The blank plasmid pcDNA3.1 (+ ) and recombinant plasmid pcDNA3.1 (+ )-BRMS1 were transfected into MG-63 cells by Lipofectamine™ 2000. Western blotting was used to detect the expression of BRMS1, nuclear factor-κB (NF-κB) p65, proliferating cell nuclear antigen (PCNA) and B cell lymphoma/leukemia-2 associated X protein (bax) protein, while methyl thiazol tetrazolium (MTT) assay and Annexin V-fluoresceine isothiocyanate (FITC)/propidium iodide (PI) double staining were used to detect cell viability and apoptosis rate, respectively. SPSS 21.0 statistical software was used for analysis. The measurement data were expressed as Mean± standard deviation (Mean±SD). T-test was used for inter-group comparison. Results The expression of BRMS1 protein in MG-63 cells after pcDNA3.1-BRMS1 transfection (0.216±0.018) was significantly higher than that in the blank group (0.018±0.004, t=33.956, P<0.05). Compared with the blank group, cell viability in pcDNA3.1-BRMS1 group and paclitaxel group (0.603±0.051, 0.536±0.04) decreased significantly (t=8.311, 11.914, P<0.05), apoptosis rate [(17.18±0.89)%, (20.02±1.07)%] increased significantly (t=48.437, 48.924, P<0.05), expression of NF-κB p65 (0.307±0.029, 0.257±0.026) decreased significantly (t=16.580, 19.403, P<0.05), expression of PCNA protein (0.222±0.021, 0.167±0.016) decreased significantly (t=7.121, 12.203, P<0.05), and expression of Bax protein (0.091±0.012, 0.131±0.013) increased significantly (t=14.352, 22.476, P<0.05). The combined use of pcDNA3.1-BRMS1 and paclitaxel had significant effects on cell viability, apoptosis and expression of NF-κB p65, PCNA and bax protein. Conclusion Overexpression of BRMS1 can inhibit the viability of osteosarcoma cells, induce apoptosis and enhance the sensitivity of paclitaxel. The mechanism is related to inhibition of NF-κB signaling pathway. Key words: Osteosarcoma; Breast cancer metastasis suppressor 1 gene; Paclitaxel sensitivity; Nuclear factor-κB signaling pathway