Influence of the MACC1 gene on sensitivity to chemotherapy in human U251 glioblastoma cells

Asian Pac J Cancer Prev. 2015;16(1):195-9. doi: 10.7314/apjcp.2015.16.1.195.

Abstract

Background: This study was conducted to determine the influence of MACC1 expression on chemotherapy sensitivity in human U251 glioblastoma cells.

Materials and methods: Expression of the MACC1 gene in 49 cases of human brain glioma was determined by quantitative real-time PCR. Silencing effects of RNA interference on MACC1 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. before and after treatment with cisplatin (DDP).

Results: MACC1 mRNA in gliomas was up-regulated remarkably, to 158.8% of that in peri-cancerous tissues (P<0.05). The siRNA-MACC1 could inhibit the expression of MACC1 protein significantly (p<0.05), associated with an increase in apoptosis rate from 2.57% to 5.39% in U251 cells and elevation of the growth inhibitory rate from 1.5% to 17.8% (p<0.05 for both). After treatment with DDP at various concentrations (1, 3, 5μg/ml), compared with control U251 cells, the apoptosis rate of MACC1-silenced U251 cells rose from 8.41%, 13.2% and 19.5% to 12.8%, 17.8% and 25.8%; the growth inhibitory rate increased from 16.2%, 19.3% and 24.5% to 23.7%, 28.4% and 36.3%.

Conclusions: There is a notable relationship between over-expression of MACC1 and the characteristics of glioma cells. Silencing of MACC1 was found to enhance the apoptosis and growth inhibitory rates of U251 glioma cells, and thereby increase their sensitivity to DDP chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cisplatin / therapeutic use*
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics*
  • Humans
  • Male
  • Middle Aged
  • Trans-Activators
  • Transcription Factors / genetics*

Substances

  • MACC1 protein, human
  • Trans-Activators
  • Transcription Factors
  • Cisplatin