Influence of the MACC1 Gene on Sensitivity to Chemotherapy in Human U251 Glioblastoma Cells


Background: This study was conducted to determine the influence of MACC1 expression on chemotherapysensitivity in human U251 glioblastoma cells. Materials and
Methods: Expression of the MACC1 gene in 49 casesof human brain glioma was determined by quantitative real-time PCR. Silencing effects of RNA interference onMACC1 was detected by Western-blotting. Flow cytometry methods and methyl thiazolyl tetrazolium assay (MTT)were used to determine the apoptosis and growth inhibitory rates of the U251 cells with MACC1 silencing. beforeand after treatment with cisplatin (DDP).
Results: MACC1 mRNA in gliomas was up-regulated remarkably, to158.8% of that in peri-cancerous tissues (P<0.05). The siRNA-MACC1 could inhibit the expression of MACC1protein significantly (p<0.05), associated with an increase in apoptosis rate from 2.57% to 5.39% in U251 cellsand elevation of the growth inhibitory rate from 1.5% to 17.8% (p<0.05 for both). After treatment with DDP atvarious concentrations (1, 3, 5μg/ml), compared with control U251 cells, the apoptosis rate of MACC1-silencedU251 cells rose from 8.41%, 13.2% and 19.5% to 12.8%, 17.8% and 25.8%; the growth inhibitory rate increasedfrom 16.2%, 19.3% and 24.5% to 23.7%, 28.4% and 36.3%.
Conclusions: There is a notable relationship betweenover-expression of MACC1 and the characteristics of glioma cells. Silencing of MACC1 was found to enhancethe apoptosis and growth inhibitory rates of U251 glioma cells, and thereby increase their sensitivity to DDPchemotherapy.