The Mechanism of Trivalent Inorganic Arsenic on HIF-1α: a Systematic Review and Meta-analysis.
Jiaqing LiuQiang NiuYunhua HuShanshan RanShu-Gang LiPublished in: Biological trace element research (2020)
The purpose of our study was to investigate the role of hypoxia-inducible factor-1α (HIF-1α) in arsenic-induced carcinogenesis. We included 39 articles for meta-analysis. The results showed that low-dose exposure to arsenic (≤ 10 μmol/L) could promote the expression of phosphatidylinositol 3-kinase (PI3K) and phosphorylation-protein kinase B (p-AKT). High-dose arsenic exposure (> 10 μmol/L) promoted the expression of PI3K, HIF-1α, vascular endothelial growth factor (VEGF), and p38MAPK (P38). Acute arsenic exposure (< 24 h) promoted the expression of PI3K, HIF-1α, and VEGF. Chronic arsenic exposure (≥ 24 h) promoted the expression of PI3K, p-AKT, and P38. Moreover, for normal tissue-derived cells, arsenic could induce the increased expression of PI3K, p-AKT, HIF-1α, and VEGF. For tumor tissue-derived cells, arsenic could induce the expression of PI3K, p-AKT, and P38. We found that arsenic exposure could activate the PI3K/AKT pathway, further induce the high expression of HIF-1α, and then upregulate the levels of miRNA-21 and VEGF, promote the expression of proliferating cell nuclear antigen (PCNA), and ultimately lead to malignant cell proliferation. Our findings indicated that arsenic could increase the expression of HIF-1α by activating the PI3K/AKT pathway and eventually induce malignant cell proliferation.
Keyphrases
- poor prognosis
- cell proliferation
- drinking water
- vascular endothelial growth factor
- endothelial cells
- low dose
- high dose
- systematic review
- signaling pathway
- binding protein
- protein kinase
- randomized controlled trial
- intensive care unit
- cell cycle
- hepatitis b virus
- drug induced
- cell death
- high glucose
- extracorporeal membrane oxygenation
- endoplasmic reticulum stress
- water soluble