Abstract
Background
Programmed cell death 5 (PDCD5) expression is reduced in various human tumor cells, and the protein concentration and nuclear translocation of PDCD5 is also observed during tumor cell apoptosis.
Aims
The purpose of this study was to investigate the differential expression of PDCD5 in six gastric cell lines, and to explore the changes of biological behavior mechanism underlying enhanced apoptosis-inducing effects of cisplatin by PDCD5 over-expression on gastric cancer BGC823 cells.
Methods
RT-PCR and real-time PCR were used to determine PDCD5 expression. BGC823/PDCD5 cells were assessed the cellular proliferating ability by MTT assay, soft agar cloning experiments and tumorigenicity in nude mice experiments in vivo. The effects of cisplatin in combination with PDCD5 on the proliferation and apoptosis were measured by MTT, Annexin-V-FITC/PI dual labeling and cell cycle analysis, respectively. Immunofluorescence was used to detect co-localization of p53 and PDCD5 protein to explore the mechanism underlying the synergistic therapeutic effect of PDCD5 with cisplatin (5 μg/ml for 24 h).
Results
PDCD5 had the highest expression level in the GES1 cell among other cell lines. The growths of BGC823 cells transfected with PDCD5 for six (6th) or 17 (17th) days were both slower than that of BGC823 and BGC823/Neo (P < 0.01). The stable transfection of PDCD5 demonstrated G2/M cell cycle arrest, increased apoptosis and nuclear translocation of PDCD5 and p53 after cisplatin treatment.
Conclusions
Stable transfection of the PDCD5 gene can inhibit the growth of the BGC823 cell line and notably improve apoptosis-inducing effects of cisplatin, indicating a novel strategy for better chemotherapeutic effects on gastric cancer.
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Acknowledgments
We are grateful to Prof. Dalong Ma and Prof. Yingyu Chen for their support of the PDCD5 antibody. We gratefully acknowledge the excellent support from all the members in Prof. Lu’s laboratory. This study was supported by grants from the National Natural Science Foundation of China (39625016), State Key Basic Research Program of China (2004CB518708), the Heilongjiang Education Department Project (Grant No. D2007-108, No. D2007-107) and the Natural Science Foundation of Heilongjiang Province (Grant No. 11531434).
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These authors have no conflict of interest.
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Xu, HY., Chen, ZW., Pan, YM. et al. Transfection of PDCD5 Effect on the Biological Behavior of Tumor Cells and Sensitized Gastric Cancer Cells to Cisplatin-Induced Apoptosis. Dig Dis Sci 57, 1847–1856 (2012). https://doi.org/10.1007/s10620-012-2090-y
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DOI: https://doi.org/10.1007/s10620-012-2090-y