Lung cancer-associated mesenchymal stem cells mediate chemoresistance and malignant progression of lung cancer through activating HIF-1α

Abstract

Background: The high mortality of lung cancer is mainly attributed to not only late detection and diagnosis but also strong invasion and the potential development of chemoresistance. This study investigated the effect and underlying mechanisms of mesenchymal stem cells (MSCs) isolated from lung cancer tissues (LC-MSCs) on lung cancer progression and chemoresistance. Methods: LC-MSCs were isolated using tissue culture method. They were characterized and verified through microscopic observation via flow cytometry (for determining MSC expression markers) and testing their ability of differentiation into adipose cells, osteocytes, or chondrocytes. Then, lung cancer A549 and H1299 cell lines cultured alone or co-cultured with LC-MSCs were used for exploring how LC-MSCs affect the progression of lung cancer cells. Temozolomide (TMZ) was administrated on differently cultured cells to determine how LC-MSCs affect the chemoresistance of lung cancer cells. Cell proliferation was evaluated by cell counting kit-8 assay, and cell cycle distribution was assessed by flow cytometry. Cell invasion, migration, and apoptosis were determined by Transwell assay, wound healing assay, and flow cytometry, respectively. Reverse transcription quantitative polymerase chain reaction, Western blot, and immunofluorescence were used to verify the upregulation of hypoxia-inducible factor-1α (HIF-1α) by LC-MSCs, and HIF-1α expression was mediated by transfection to investigate the effect of HIF-1α on lung ca…