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Transfection of PDCD5 Effect on the Biological Behavior of Tumor Cells and Sensitized Gastric Cancer Cells to Cisplatin-Induced Apoptosis

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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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References

  1. Andrews PA, Howell SB. Cellular pharmacology of cisplatin: perspectives on mechanisms of acquired resistance. Cancer Cells. 1990;2:35–43.

    PubMed  CAS  Google Scholar 

  2. Andrews PA, Jones JA, Varki NM, Howell SB. Rapid emergence of acquired cis-diammine- dichloroplatinum (II) resistance in an in vivo model of human ovarian carcinoma. Cancer Commun. 1990;2:93–100.

    PubMed  CAS  Google Scholar 

  3. Andrews PA, Schiefer MA, Murphy MP, Howell SB. Enhanced potentiation of cisplatin cytotoxicity in human ovarian carcinoma cells by prolonged glutathione depletion. Chem Biol Interact. 1988;65:51–58.

    Article  PubMed  CAS  Google Scholar 

  4. Marverti G, Cusumano M, Ligabue A, et al. Studies on the anti-proliferative effects of novel DNA-intercalating bipyridyl-thiourea-Pt(II) complexes against cisplatin-sensitive and -resistant human ovarian cancer cells. J Inorg Biochem. 2008;102:699–712.

    Article  PubMed  CAS  Google Scholar 

  5. Liu H, Wang Y, Zhang Y, et al. TFAR19, a novel apoptosis-related gene cloned from human leukemia cell line TF-1, could enhance apoptosis of some tumor cells induced by growth factor withdrawal. Biochem Biophys Res Commun. 1999;254:203–210.

    Article  PubMed  CAS  Google Scholar 

  6. Yang YH, Zhao M, Li WM, et al. Expression of programmed cell death 5 gene involves in regulation of apoptosis in gastric tumor cells. Apoptosis. 2006;11:993–1001.

    Article  PubMed  CAS  Google Scholar 

  7. Chen Y, Sun R, Han W, et al. Nuclear translocation of PDCD5 (TFAR19): an early signal for apoptosis? FEBS Lett. 2001;509:191–196.

    Article  PubMed  CAS  Google Scholar 

  8. Spinola M, Meyer P, Kammerer S, et al. Association of the PDCD5 locus with lung cancer risk and prognosis in smokers. J Clin Oncol. 2006;24:1672–1678.

    Article  PubMed  CAS  Google Scholar 

  9. Li SJ, Yu J, Zhao XF, Jiang Y, Liu ZJ, Yu XG. PDCD5 induces the apoptosis of human prostate cancer cells PC-3M-1E8. Zhonghua Nan Ke Xue. 2007;13:979–982.

    PubMed  CAS  Google Scholar 

  10. Du YJ, Xiong L, Lou Y, Tan WL, Zheng SB. Reduced expression of programmed cell death 5 protein in tissue of human prostate cancer. Chin Med Sci J. 2009;24:241–245.

    Article  PubMed  Google Scholar 

  11. Liu ZH, Zhang D, Li KM, Liao QP. Expression of PDCD5 in tissues of normal cervix, CIN I-III and cervical cancer. Beijing Da Xue Xue Bao. 2004;36:407–410.

    PubMed  Google Scholar 

  12. Ruan GR, Zhao HS, Chang Y, et al. Adenovirus-mediated PDCD5 gene transfer sensitizes K562 cells to apoptosis induced by idarubicin in vitro and in vivo. Apoptosis. 2008;13:641–648.

    Article  PubMed  CAS  Google Scholar 

  13. Su DM, Zhang Q, Wang X, et al. Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy. Mol Cancer Ther. 2009;8:1–13.

    Article  CAS  Google Scholar 

  14. Zhao XY, Liu HW, Wei MJ. Expressions of PDCD5 and p53 in oral leukoplakia and oral squamous cell carcinoma. Beijing Da Xue Xue Bao. 2005;37:429–432.

    PubMed  CAS  Google Scholar 

  15. Ke Y, Ning T, Wang B. Establishment and characterization of a SV40 transformed human fetal gastric epithelial cell line-GES-1. Zhonghua Zhong Liu Za Zhi. 1994;16:7–10.

    PubMed  CAS  Google Scholar 

  16. Kajiwara Y, Panchabhai S, Levin VA. A new preclinical 3-dimensional agarose colony formation assay. Technol Cancer Res Treat. 2008;7:329–334.

    PubMed  Google Scholar 

  17. Tsai MH, Aki R, Amoh Y, et al. GFP-fluorescence-guided UVC irradiation inhibits melanoma growth and angiogenesis in nude mice. Anticancer Res. 2010;30:3291–3294.

    PubMed  Google Scholar 

  18. Bergeron S, Lemieux E, Durand V, et al. The serine protease inhibitor serpinE2 is a novel target of ERK signaling involved in human colorectal tumorigenesis. Mol Cancer. 2010;9:271.

    Article  PubMed  Google Scholar 

  19. Li H, Wang Q, Gao F, et al. Reduced expression of PDCD5 is associated with high-grade astrocytic gliomas. Oncol Rep. 2008;20:573–579.

    PubMed  CAS  Google Scholar 

  20. Chen C, Zhou H, Xu L, et al. Prognostic significance of downregulated expression of programmed cell death 5 in chondrosarcoma. J Surg Oncol. 2010;102:838–843.

    Article  PubMed  CAS  Google Scholar 

  21. Zhang X, Wang X, Song X, et al. Clinical and prognostic significance of lost or decreased PDCD5 expression in human epithelial ovarian carcinomas. Oncol Rep. 2011;25:353–358.

    PubMed  CAS  Google Scholar 

  22. Matsuhashi N, Saio M, Matsuo A, Sugiyama Y, Saji S. Apoptosis induced by 5-fluorouracil, cisplatin and paclitaxel are associated with p53 gene status in gastric cancer cell lines. Int J Oncol. 2005;26:1563–1567.

    PubMed  CAS  Google Scholar 

  23. Chen C, Zhou H, Xu L, et al. Recombinant human PDCD5 sensitizes chondrosarcomas to cisplatin chemotherapy in vitro and in vivo. Apoptosis. 2010;15:805–813.

    Article  PubMed  CAS  Google Scholar 

  24. Shi L, Song Q, Zhang Y, et al. Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells. Biochem Biophys Res Commun. 2010;396:224–230.

    Article  PubMed  CAS  Google Scholar 

  25. Yin A, Jiang Y, Zhang X, Zhao J, Luo H. Transfection of PDCD5 sensitizes colorectal cancer cells to cisplatin-induced apoptosis in vitro and in vivo. Eur J Pharmacol. 2010;649:120–126.

    Article  PubMed  CAS  Google Scholar 

  26. Kim R, Emi M, Tanabe K, Toge T. Preclinical evaluation of antisense bcl-2 as a chemosensitizer for patients with gastric carcinoma. Cancer. 2004;101:2177–2186.

    Article  PubMed  CAS  Google Scholar 

  27. Cho HJ, Baek KE, Park SM, et al. RhoGDI2 confers gastric cancer cells resistance against cisplatin-induced apoptosis by upregulation of Bcl-2 expression. Cancer Lett. 2011;311:48–56.

    Article  PubMed  CAS  Google Scholar 

  28. Ando T, Kawabe T, Ohara H, Ducommun B, Itoh M, Okamoto T. Involvement of the interaction between p21 and proliferating cell nuclear antigen for the maintenance of G2/M arrest after DNA damage. J Biol Chem. 2001;276:42971–42977.

    Article  PubMed  CAS  Google Scholar 

  29. Selvendiran K, Tong L, Vishwanath S, et al. EF24 induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by increasing PTEN expression. J Biol Chem. 2007;282:28609–28618.

    Article  PubMed  CAS  Google Scholar 

  30. Allday MJ, Inman GJ, Crawford DH, Farrell PJ. DNA damage in human B cells can induce apoptosis, proceeding from G1/S when p53 is transactivation competent and G2/M when it is transactivation defective. EMBO J. 1995;14:4994–5005.

    PubMed  CAS  Google Scholar 

  31. Brown R, Clugston C, Burns P, et al. Increased accumulation of p53 protein in cisplatin-resistant ovarian cell lines. Int J Cancer. 1993;55:678–684.

    Article  PubMed  CAS  Google Scholar 

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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).

Conflict of interest

These authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Immunology, Qiqihar Medical University, No.333 BuKui Street Jianhua District, Qiqihar, 161006, Heilongjiang, People’s Republic of China

    Hui-Yu Xu, Zhi-Wei Chen, Li Fan & Jie Guan

  2. Laboratory of Molecular Oncology, Beijing Cancer Hospital/Institute, School of Oncology, Peking University, 52 Fu-Cheng Road, Hai-Dian District, Beijing, 100142, People’s Republic of China

    Yuan-Ming Pan & You-Yong Lu

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  1. Hui-Yu Xu
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  2. Zhi-Wei Chen
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  3. Yuan-Ming Pan
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  4. Li Fan
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Correspondence to Zhi-Wei Chen or You-Yong Lu.

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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

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