Abstract:
The cell-cycle related genes are potential gene targets in understanding the
effects of efavirenz (EFV) in lung cancer. The present study aimed at investigating
the expression changes of cell-cycle related genes in response to EFV drug treatment
in human non-small cell lung carcinoma (A549) and normal lung fibroblast (MRC-5)
cells. The loss in nuclear integrity in response to EFV was detected by 4′, 6-diamidino2-phenylindole (DAPI) staining. Gene expression profiling was performed using
human cell cycle PathwayFinder RT2 Profiler™ PCR Array. The expression changes
of 84 genes key to the cell cycle pathway in humans following EFV treatment was
examined. The R2 PCR Array analysis revealed a change in expression of selected
gene targets (including MAD2L2, CASP3, AURKB). This change in gene expression was
at least a two-fold between test (EFV treated) and the control. RT-qPCR confirmed
the PCR array data. In addition to this, the ATM signaling pathway was shown to be
upregulated following EFV treatment in MRC-5 cells. In particular, ATM’s upstream
activation resulted in p53 upregulation in normal lung fibroblasts. Interestingly, the
p53 signaling pathway was activated irrespective of the repressed ATM pathway in
A549 cells as revealed by the Ingenuity Pathway Analysis (IPA). These EFV effects
are similar to those of ionizing radiation and this suggests that EFV has anti-tumour
properties.
