1 research outputs found
Identification of Up- and Down-Regulated Proteins in Pemetrexed-Resistant Human Lung Adenocarcinoma: Flavin Reductase and Calreticulin Play Key Roles in the Development of Pemetrexed-Associated Resistance
Drug
resistance is one of the major causes of cancer chemotherapy
failure. In the current study, we used a pair of lung adenocarcinoma
cell lines, A549 and the pemetrexed-resistant A549/PEM cells, as a
model to monitor resistance-dependent cellular responses and identify
potential therapeutic targets. By means of 2D differential gel electrophoresis
(2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight
mass spectrometry (MALDI-TOF MS), we investigated the global protein
expression alterations induced by pemetrexed treatment and resistance.
The proteomic result revealed that pemetrexed exposure obviously altered
the expression of 81 proteins in the A549 cells, whereas no significant
response was observed in the similarly treated A549/PEM cells, hence
implying an association between these proteins and the drug-specific
response. Moreover, 72 proteins including flavin reductase and calreticulin
demonstrated differential expression between the A549 and A549/PEM
cells, indicating baseline resistance. Additional tests employed siRNA
silencing, protein overexpression, cell viability analysis, and analysis
of apoptosis to examine and confirm the potency of flavin reductase
and calreticulin proteins in the development of pemetrexed resistance.
In summary, by using a proteomic approach, we identified numerous
proteins, including flavin reductase and calreticulin, involved in
pemetrexed drug resistance-developing mechanisms. Our results provide
useful diagnostic markers and therapeutic candidates for pemetrexed-resistant
lung cancer treatment