PRDX3 promotes resistance to cisplatin in gastric cancer cells

Objective: This study aims to investigate peroxiredoxin 3 (PRDX3) expression in gastric cancer tissue and its effects on cisplatin resistance in gastric cancer cells and its possible mechanism. Methods: PRDX3 expression in human gastric cancer tissue microarrays was detected via immunohistochemistry. The PRDX3 small interfering RNA (siPRDX3 group) and the negative control siNC (siNC group) were transfected into AGS and MKN-74 cell lines, respectively, whereas a blank control group was set up. Each group was treated with different cisplatin concentrations (0, 5, 10, 15, 20, 25, and 30 mu g/ml), and the half-inhibitory concentration (IC50) of each group of the two cell lines was calculated using the CCK8 assay. The corresponding IC50 concentration of the siPRDX3 group in the two cell lines was used to treat cells of each group. Flow cytometry was used to detect cell apoptosis, and Western blotting was used to detect the expression levels of cleaved caspase-3 and Bax in each group. Results: PRDX3 was overexpressed in gastric adenocarcinoma tissue compared with adjacent noncancer tissue (P = 0.0053). After cisplatin treatment, the IC50 in the siPRDX3 group of AGS cells (5.91 +/- 0.18 mu g/ml) and the siPRDX3 group of MKN-74 cells (3.48 +/- 0.30 mu g/ml) was significantly lower than in the corresponding siNC groups (10.01 +/- 0.99 and 6.39 +/- 0.70 mu g/ml; P = 0.0022 and 0.0027, respectively). AGS cells (38.81% +/- 1.69%) and MKN-74 cells (25.03% +/- 2.80%) in the siPRDX3 group showed significantly higher apoptosis rates than in the corresponding siNC groups (23.17% +/- 1.43% and 16.7% +/- 1.39%; P = 0.0003 and 0.0099, respectively). The expression levels of cleaved caspase-3 and Bax were significantly higher in the siPRDX3 group of both cell lines than in the siNC group (P < 0.0001). Conclusion: PRDX3 increases the gastric cancer cell resistance to cisplatin by reducing apoptosis and thus may serve as a target to overcome cisplatin resistance.