[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.


CONCLUSIONS
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.
Department of Thoracic Surgery, Ningxia Medical University, Yinchuan 750004, China.
Jinxi
J
He
Institute of Laboratory Medicine, Ningxia Human Stem Cell Institute, Ningxia Medical University, Yinchuan 750004, China.
Xumei
X
Song
Department of Thoracic Surgery, Ningxia Medical University, Yinchuan 750004, China.
Liang
L
Yu
Department of Thoracic Surgery, Ningxia Medical University, Yinchuan 750004, China.
Jing
J
Li
Department of Thoracic Surgery, Ningxia Medical University, Yinchuan 750004, China.
Zhixiong
Z
Qiao
Department of Thoracic Surgery, Ningxia Medical University, Yinchuan 750004, China.
Rui
R
Jiu
Department of Thoracic Surgery, Ningxia Medical University, Yinchuan 750004, China.
Bo
B
Yu
Ningxia Human Stem Cell Institute, Ningxia Medical University, Yinchuan 750004, China.
Xiaoming
X
Liu
D000230:Adenocarcinoma / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000445:Aldehyde Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D007527:Isoenzymes; D012333:RNA, Messenger; D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+); D002945:Cisplatin