ac7b00218_si_001.pdf (1.93 MB)
Signal Transductions of BEAS-2B Cells in Response to Carcinogenic PM2.5 Exposure Based on a Microfluidic System
journal contribution
posted on 2017-04-27, 00:00 authored by 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, Guodong SuiPM2.5 (particulate matter less than 2.5 μm 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 an 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 be uptaken into the cells by pinocytosis, mainly promoting the
PI3K-Akt pathway, FGF/FGFR/MAPK/VEGF signaling, and the 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 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 of organics (OC, PAHs) and
metals (Zn, As, V) that 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.