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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 μg/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 μg/ml) and the siPRDX3 group of MKN-74 cells (3.48 ± 0.30 μg/ml) was significantly lower than in the corresponding siNC groups (10.01 ± 0.99 and 6.39 ± 0.70 μg/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. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy is the only therapy option for the majority of AML patients, however, there are several limitations for this treatment. Our aim was to find a new chemotherapy strategy that is more effective and less toxic. Methods: MTT assays and a xenograft mouse model were employed to evaluate the synergistic activity of all-trans retinoic acid (ATRA) combined with topotecan (TPT). Drug-induced DNA damage and apoptosis were determined by flow cytometry analysis with PI and DAPI staining, the comet assay and Western blots. Short hairpin RNA (shRNA) and a RARα plasmid were used to determine whether RARα expression influenced DNA damage and apoptosis. Results: We found that ATRA exhibited synergistic activity in combination with Topotecan in AML cells, and the enhanced apoptosis induced by Topotecan plus ATRA resulted from caspase pathway activation. Mechanistically, ATRA dramatically down regulated RARα protein levels and led to more DNA damage and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of Topotecan combined with ATRA was further validated in the HL60 xenograft mouse model. Conclusions: Our data demonstrated, for the first time, that the combination of TPT and ATRA showed potential benefits in AML, providing a novel insight into clinical treatment strategies. [ABSTRACT FROM AUTHOR]