我们的研究目的是探讨缺氧诱导因子-1α（HIF-1α）在砷诱导的致癌作用。我们纳入了39篇文章进行荟萃分析。结果表明，低剂量砷（≤10μmol/L）可促进磷脂酰肌醇3激酶（PI3K）和磷酸化蛋白激酶B（p-AKT）的表达。高剂量砷暴露(>10μmol/L)促进PI3K的表达,HIF-1α,血管内皮生长因子（VEGF），和p38MAPK（P38）。急性砷暴露（<24h）促进PI3K的表达，HIF-1α,和VEGF。慢性砷暴露（≥24h）促进PI3K的表达，p-AKT,P38此外，对于正常组织来源的细胞，砷可以诱导PI3K的表达增加，p-AKT,HIF-1α,和VEGF。对于肿瘤组织来源的细胞，砷可以诱导PI3K的表达，p-AKT,P38我们发现砷暴露可以激活PI3K/AKT通路，进一步诱导HIF-1α的高表达，然后上调miRNA-21和VEGF的水平，促进增殖细胞核抗原（PCNA）的表达，并最终导致恶性细胞增殖。我们的发现表明，砷可以通过激活PI3K/AKT通路增加HIF-1α的表达，最终诱导恶性细胞增殖。
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.
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