Antisense oligodeoxynucleotides against thrombomodulin suppress the cell growth of lung adenocarcinoma cell line A549.

Thrombomodulin (TM), an anticoagulant factor on endothelial cells, is known to be expressed in non-endothelial cells as well. In neoplastic cells of lung adenocarcinomas, TM is expressed but its correlation with growth potential has not been studied. As TM expression has a negative correlation with cell proliferation in lung squamous cell carcinomas, we examined its growth effect on lung adenocarcinoma cells of the A549 cell line by inhibiting TM expression with antisense oligodeoxynucleotides (ODN). In the antisense ODN transfected cells, the expression of TM mRNA was decreased to 49% at 12 h and 47% at 24 h, which was in accordance with TM expression at the protein level. By IdU (5-iodo-2'-deoxyuridine) incorporation assay, the growth of A549 cells was found to have decreased to 36% of the control level at 24 h post-transfection. The suppression of cell growth was maintained in a concentration-dependent manner for 48 h after transfection, when the expression of TM started to rebound. In the transfected cells, the G1 phase cell count was reduced to 60.7%, compared with 68.2% in the control transfectants. These results suggest that TM expression may play a suppressive role in the proliferation activity of A549 lung adenocarcinoma cells.