Hypoxia-inducible factor 1α (HIF1α) has been demonstrated to be involved in the resistance of various human
cancer cells to
chemotherapies. However, the correlation between HIF1α and the sensitivity of human
non-small cell lung cancer (NSCLC) cells to
cisplatin has not been illuminated. The aim of the present study was to investigate the effects of HIF1α on drug resistance in NSCLC cells. A549 cells were incubated in 21% or 0.5% O2 followed by the assessment of the level of HIF1α with qRT-PCR and western blot and ROS level by
DCFH-DA assays. Effects of
hypoxia or HIF1α inhibitor LW6 on the proliferation and apoptosis of A549 cells were evaluated via
CCK-8 and flow cytometry assays. IC50 of A549 cells to
cisplatin was determined by MTT assay. The mitochondrial membrane potential (
MMP) was measured via
JC-1 staining. Moreover, the expression of apoptosis related
protein (Bcl-2, Bax) and drug resistance related
proteins (MDR1,
MRP1) were measured by western blotting. Exposure of A549 cells to 1% O2 significantly up-regulated HIF1α expression, maintained cell viability to
cisplatin but decreased the ROS level, which promoted chemoresistance to
cisplatin. LW6-treated A549 cells showed an increase in ROS level that blocked the
hypoxia induced resistance to
cisplatin and in addition, decreased expression of MDR1 and
MRP1 in
cisplatin-treated cells. This study revealed that
hypoxia-improved
cisplatin chemoresistance of NSCLC cells by regulated MDR1 and
MRP1 expression via HIF1α/ROS pathway is reversed by LW6, suggesting that LW6 may act as effective sensitizer in
chemotherapy for NSCLC.