[Analytical Chemistry] Signal Transductions of BEAS-2B Cells in Response to Carcinogenic PM2.5 Expos
PM2.5 (particulate matter less than 2.5 micrometers in diameter) is considered as a harmful carcinogen. Determining the precise relationship between the chemical constituents of PM2.5 in the air and cancer progression could aid the treatment of environment related disease and establishing risk reduction strategies. Herein, we used transcriptomics (RNA-seq) and integrated microfluidic system to identify the global gene expression and differential target proteins expression induced by ambient fine particles collected from the heavy haze in China. The results clearly indicated that cancer related pathways exhibited the strongest dysregulation. The ambient fine particles could uptake into the cells by pinocytosis, mainly promoting the PI3K-Akt pathway, FGF/FGFR/MAPK/VEGF signaling, and JAK-STAT pathway, leading to evading apoptosis, sustained angiogenesis, and cell proliferation, which are the most important hallmarks of cancer. And fine particles also have been demonstrated to create intracellular reactive oxygen species (ROS) and mitochondrial ROS, change intracellular free Ca2+, and induce apoptosis, which are all key players in mediating cancer progression. It was observed by Transmission Electron Microscopy (TEM) that the particles from the haze could enter the mitochondria, resulting in the disturbance of the mitochondrial membrane and disruption of the mitochondria, and these particles can even enter inside the nucleus. It was also found in our study Organic (OC, PAHs) and metals (Zn, As, V) compounds of fine particles were more closely associated with the exacerbation of cancer and secondary aerosols generated by traffic had the largest impact on cancer related signal transductions.
Lulu Zheng, Sixiu Liu, Guoshun Zhuang, Jian Xu, Qi Liu, Xinlian Zhang, Congrui Deng, Zhigang Guo, Wang Zhao, Tingna Liu, Yiqi Wang, Yuxiao Zhang, Jing Lin, Qiongzhen Wang, and Guodong Sui Anal. Chem., Just Accepted Manuscript DOI: 10.1021/acs.analchem.7b00218 Publication Date (Web): April 27, 2017 Copyright © 2017 American Chemical Society