Abstract
Purpose: Arsenic has been reported to induce apoptosis in malignant tumor cells, therefore, it may be regarded as a treatment for some cancers. The mitochondrial apoptosis pathway, mediated by GSK-3β, plays an important role in tumor cell apoptosis. Nonetheless, the regulation of GSK-3β by arsenic remains controversial. Materials and Methods: We included 19 articles, which conducts the role of GSK-3β in the process of arsenic-induced tumor cell apoptosis by the meta-analysis. Results: Compared with the control group, the expression of GSK-3β (SMD=-0.92,95% CI (-1.78,-0.06)), p-Akt (SMD=-5.46,95% CI (-8.67,-2.24)) were reduced in the arsenic intervention group. Meanwhile, the combined treatment of arsenic and Akt agonist can inhibit the expression of p-GSK-3β. Using the dose and time subgroup analysis, it was shown that the low-dose and sub-chronic arsenic exposure could inhibit the expression of p-Akt (P<0.05). In the subgroup analysis of GSK-3β sites, arsenic could inhibit p-Akt and GSK-3β (Ser9) (SMD =-0.95, 95% CI (-1.56,-0.33)). There was a dose-related effect seen between arsenic (≤8 μmol/L) and p-GSK-3β, and the expression of p-GSK-3β was gradually followed by the arsenic dose. When arsenic acted on GSK-3β (ser9), the expression of Mcl-1 and pro-caspase-3 were dropped, while the loss rate of mitochondrial membrane potential and cleaved-caspase-3 were increased significantly (P<0.05). Conclusion: This study revealed that arsenic could inhibit the expression of GSK-3β (Ser9) and then induce tumor cell apoptosis. It might be correlated with arsenic inhibiting p-Akt, down-regulating GSK-3β, and triggering the Mcl-1-mediated mitochondrial apoptosis pathway.
Correction: Galectin-3 Silencing Inhibits Epirubicin-Induced ATP Binding Cassette Transporters and Activates the Mitochondrial Apoptosis Pathway via β-Catenin/GSK-3β Modulation in Colorectal Carcinoma