Abstract
Objectives
Malignant cell proliferation is one of the important mechanisms of arsenic poisoning. A large number of studies have shown that STAT3 plays an important role in cell malignant proliferation, but there are still many contradictions in the effect of arsenic on JAK2/STAT3. This study aims to explore the role of JAK2/STAT3 in arsenic-induced cell proliferation.
Methods
By taking normal cells as the research object and using Standard Mean Difference (SMD) as the effect size, meta-analysis was used to explore the effect of arsenic on JAK2/STAT3. Then, the dose-effect Meta was used to further clarify the dose-effect relationship of arsenic on JAK2/STAT3.
Results
Through meta-analysis, this study found that arsenic could promote the phosphorylation of STAT3 (SMD=4.21, 95%CI [1.05, 7.37]), and increase IL-6 and p-JAK2, Vimentin, VEGF expression levels, thereby inducing malignant cell proliferation. In addition, this study also found that arsenic exposure dose (<5 μmol m−3), time(<24 h) and cell type were important sources of heterogeneity in the process of exploring the effects of arsenic on p-STAT3, IL-6 and p-JAK2. Dose-effect relationship meta-analysis results showed that arsenic exposure significantly increased the expression level of IL-6. When the arsenic exposure concentration was less than 7 μmol m−3, the expression level of p-JAK2 upregulated significantly as the arsenic exposure concentration gradually increasing. Moreover, the expression level of p-STAT3 elevated significantly with the gradual increase of the arsenic concentration under 5 μmol m−3 of arsenic exposure, but the expression level of p-STAT3 gradually decreases when the concentration is greater than 5 μmol m−3.
Conclusions
Exposure to low dose of arsenic could promote the expression of JAK2/STAT3 and induce the malignant proliferation of cells through upregulating IL-6, and there was dose-effect relationship among them.
Fourier methods for recursive estimating of distribution function in dose-effect relationship
