[Increased expression of acetaldehyde dehydrogenase in cisplatin-resistant human lung adenocarcinoma A549/DDP cells].

OBJECTIVE

To investigate the expression and biological significance of acetaldehyde dehydrogenase (ALDH) in cisplatin-resistant human A549/DDP lung adenocarcinoma cell line.

METHODS

The expressions of biomarkers of cancer stem cells (CSCs) including CD44, CD73, CD90, CD105, epithelial cell adhesion molecule (EpCAM), ATP-binding cassette sub-family G member 2 (ABCG2) and ALDH in human lung adenocarcinoma A549 cells and cisplatin-resistant A549/DDP cells were ascertained by flow cytometry. The proliferation and sensitivity of A549/DDP cells to cisplatin were evaluated by MTT assay before and after ALDH inhibitor diethylaminobenzaldehyde (DEAB) treatment. The differential expression of ALDH subtypes in cells was determined by real-time quantitative PCR, and was further confirmed by a Western blotting.

RESULTS

The frequencies of ABCG2 and ALDH positive cells were higher in cisplatin-resistant A549/DDP cells than those in A549 cells, in particular the expression of ALDH which was 97.7% in A549/DDP cells, and only 4.3% in A549 cells. There was no significantly differential expression of CD44, CD90, CD73, CD105 between A549/DDP cells and A549 cells, whereas less EpCAM was found in A549/DDP cells compared with A549 cells. Importantly, the ALDH inhibitor DEAB (100 μmol/L) was able to significantly reduce cisplatin resistance in A549/DDP cells. Compared with A549 cells, the expressions of ALDH subtypes ALDH1A3 and ALDH1B1 mRNA significantly went up in A549/DDP cells. Interestedly, Western blotting revealed that ALDH1B1 protein expression was elevated but ALDH1A3 protein was reduced in A549/DDP cells in comparison with A549 cells.

CONCLUSION

ALDH can serve as a useful surface marker for cisplatin-resistant human lung adenocarcinoma cells.ALDH1B1 may play a role in the chemoresistance of these cells. Therefore, ALDH1B1 may be an important target for developing novel therapeutic agents and strategies for patients with cisplatin-resistant lung adenocarcinoma.